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WELCOME TO THE CLINICAL
CENTER GRAND ROUNDS,

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A WEEKLY SERIES OF EDUCATIONAL
LECTURES FOR PHYSICIANS AND

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HEALTH CARE PROFESSIONALS
BROADCAST FROM THE CLINICAL

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CENTER AT THE NATIONAL
INSTITUTES OF HEALTH IN

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BETHESDA, MD.

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THE NIH CLINICAL CENTER IS THE
WORLD'S LARGEST HOSPITAL TOTALLY

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DEDICATED TO INVESTIGATIONAL
RESEARCH AND LEADS THE GLOBAL

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EFFORT IN TRAINING TODAY'S
INVESTIGATORS AND DISCOVERING

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TOMORROW'S CURES.

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LEARN MORE BY VISITING US ONLINE
AT HTTP://CLINICALCENTER.NIH.GOV

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GOOD MORNING, I'M ELIZABETH 

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JONES OF CHIEF OF RADIOLOGY AND 

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IMAGING SCIENCES AND I'M PLEASED

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TO WELCOME YOU TO TODAY'S LIVE 

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VIRTUAL GRAND ROUNDS.  WHICH IS 

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THE JOHN MEMORIAL LECTURE FOR 

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IMAGING SCIENCES.  THE HOPKINS 

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CODE FOR TODAY IS 57876 TEXT 

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THIS CODE TO THE JOHNS HOPKINS 

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CME PHONE NUMBER ON THE SLIDE TO

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RECEIVE CME CREDIT AND WE KINDLY

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INVITE YOU TO PROVIDE FEEDBACK 

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ON TODAY'S LECTURE BY SCANNING 

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THE QR CODE ON THE CME SLIDE FOR

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THOSE APPLYING FOR CME WILL 

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RECEIVE A FEEDBACK SURVEY LINK 

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VIA E-MAIL AFTER THE LECTURE THE

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SURVEY'S USED TO PROVIDE US WITH

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IMPORTANT FEEDBACK ABOUT THE 

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PRESENTATION AND ALLOWS YOU TO 

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SUBMIT ANY SUGGESTIONS FOR 

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FUTURE TOPICS AT GRAND ROUNDS 

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FOLLOWING THE PRESENTATION, 

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QUESTIONS FOR THE SPEAKER WILL 

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BE TAKEN FROM THE MICROPHONES IN

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THE AISLES, AADDITIONALLY VIDEO 

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CAST VIEWERS CAN ASK QUESTIONS 

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AT ANY TIME.  QUESTIONS WILL BE 

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ANSWERED AS TIME PERMITS AT THE 

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CONCLUSION OF THE PRESENTATION. 

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DR. WOODARD CHAIRS THE 

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DEPARTMENT OF RADIOLOGY AND 

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DIRECTS THE INSTITUTE OF 

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RADIOLOGY IN ST. LOUIS WHERE SHE

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ALSO SERVES AS THE ELIZABETH E 

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PROFESSOR OF RADIOLOGY AND A 

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PROFESSOR OF MEDICINE, 

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PEDIATRICS AND BIOMEDICAL 

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ENGINEERING, EARNED HER BACHELOR

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OF ARTS AT DUKE UNIVERSITY AND 

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HER MEDICAL DEGREE AT DUKE 

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UNIVERSITY SCHOOL OF MEDICINE, 

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COMPLETED HER INTERNSHIP AT THE 

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UNIVERSITY OF NORTH CAROLINA AT 

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CHAPEL HILL AND A RESIDENCY?  

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DIAGNOSTIC RADIOLOGY AS DUKE 

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UNIVERSITY MEDICAL CENTER. 

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SHE THEN COMPLETED HER 

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FELLOWSHIP AT THE INSTITUTE OF 

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RADIOLOGY AT THE WASHINGTON 

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SCHOOL OF MEDICINE AND WAS 

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APPOINTED TO THE FACULTY THERE 

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IN 1997.  DR. WOODARD IS 

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WELL-KNOWN FOR HER IMPORTANT 

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CONTRIBUTIONS IN CARDIOVASCULAR 

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RESEARCH, PARTICULARLY IN 

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TRANSLATING NEW IMAGING 

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PROCEDURE TO CLINICAL CARE.  

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IN 1995, WHILE STILL A RESIDENT 

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AT DUKE, DR. WOODARD PUBLISHED 

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ONE OF THE FIRST PAPERS 

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DEMONSTRATING THAT PULMONARY 

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EMBOLI COULD BE DETECTED.  

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AND LATER SERVED AS PI ON AN NIH

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FUNDING CLINICAL TRIAL THAT 

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RESULTED IN A LANDMARK NEW 

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ENGLAND JOURNAL OF MEDICINE 

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PAPER ESTABLISHING MULTIDETECTER

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CT AS THE CENTER OF CARE FOR 

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FINDING PULMONARY EMBOLI.  TODAY

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HE SERVES ON GRANTS.  ALL WITH A

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FOCUS ON CARDIOVASCULAR IMAGING 

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IN ADDITION SHE SERVES AS THE 

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PROGRAM DIRECTOR FOR THE NIH, 

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NATIONAL INSTITUTE OF BIOMEDICAL

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ENGINEERING AND FUNDED T32 

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CLINICIAN SCIENCE GRANT CALLED 

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TOP TIER AT WASHINGTON 

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UNIVERSITY.  DR. WOODARD WAS 

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NAMED THE 2021 OUTSTANDING 

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RESEARCHER BY THE RSNA, 

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RADIOLOGIC SOCIETY OF AMERICA 

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AND IS A FELLOW OF THE AMERICAN 

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ASSOCIATION FOR THE ADVANCEMENT 

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OF SCIENCE.  SHE IS CURRENTLY 

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VICE PRESIDENT OF THE ACADEMY OF

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RADIOLOGY AND BIOMEDICAL IMAGING

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RESEARCH AND THE CURRENT 

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PRESIDENT OF THE AMERICAN 

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COLLEGE OF RADIOLOGY.  

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THE TITLE OF TODAY'S 

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PRESENTATION IS PRECISION PET, 

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TRANSLATIONAL IMAGING AND 

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BUILDING THE NEXT GENERATION OF 

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CLINICIAN SCIENTISTS PLEASE 

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WELCOME ME IN JOINING OUR 

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SPEAKER, DR. WOODARD.

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>> WELL, ELIZABETH, THANK
YOU 

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VERY MUCH FOR THAT EXCELLENT 

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PRESENTATION OR ANNOUNCEMENT.  I

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REALLY, YOU KNOW, FEEL HONORED 

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TO BE HERE AND I'M REALLY 

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DELIGHTED TO BE SPEAKING TO YOU 

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ALL.  IT'S VERY EXCITING.  I WAS

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ABLE TO SEE A LOT OF INTERESTING

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RESEARCH AND EXCITING CUTTING 

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EDGE LOW FIELD STRENGTH MMRI 

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RESEARCH THIS MORNING.  WE ARE 

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HERE TODAY TO HONOR JOHN, BY ALL

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ACCOUNTS WAS A REMARKABLE 

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RADIOLOGIST AND INTERVENTIONAL 

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RADIOLOGIST AND HERE ARE MY 

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DISCLOSURES.  DR. DEVELOP MAN 

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PASSED AWAY IN 2000 BUT WAS HERE

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AT THE NIH FOR 26 YEARS.  

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AS THE DIRECTOR OF THE WARREN 

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GRANT MAGNUSON CLINICAL CENTER 

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MORE INSTITUTES OF HEALTH. 

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ARRIVED AT NIH THE YEAR I WAS 

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BORN AND BECAME CHIEF OF 

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RADIOLOGY IN 1972. 

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AND BROUGHT NEW TECHNOLOGY TO 

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THE DEPARTMENT.  CT AND MRI 

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SCANNERS WHICH AT THE TIME WERE 

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THE CUTTING EDGE, YOU KNOW, JUST

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THE VERY FIRST SCANNERS COMING 

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IN IN THE 70S AND THEN IN THE 

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80S WITH MRI.  AS AN 

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INTERVENTIONAL RADIOLOGIST HE 

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WAS A PIONEER, HE INVENTED AND 

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PERFORMED MANY DIAGNOSTIC 

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PROCEDURES, MANY THERAPEUTIC 

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PROCEDURES SPECIFICALLY IN 

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LOCALIZATION AND TREATMENT OF 

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ENDOCRINE TUMORS.  THIS IS HIS 

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ARTICLE THAT CAME OUT IN 

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RADIOLOGY IN 1970S.  AND ALSO, 

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WAS INSTRUMENTAL IN STUDYING AND

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IMAGING AND TREATING AVMS AND 

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FISTULAS OF THE SPINE AND SPINAL

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CORD.  HE LOVED RADIOLOGY, HE 

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HAD 516 PAPERS.  AND 38 BOOK 

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CHAPTERS.  HAD GOLD MEDALS FROM 

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THE RANKIN RAY AND SUIVR, EDITOR

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AND CONSULTING EDITOR OF 

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NUMEROUS JOURNALS.  YOU KNOW, 

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NOT JUST ONE OR TWO.  AND HE WAS

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CALLED A TRIPLE THREAT.  A 

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SUPERB TEACHER, AND AN ASTUTE 

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CLINICIAN, SO I'M DELIGHTED TO 

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BE HELPING YOU REMEMBER HIS 

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LEGACY TODAY.  I'M GOING TO TALK

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TO YOU ABOUT PRECISION PET 

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TRANSLATIONAL IMAGING AND 

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BUILDING THE NEXT GENERATION OF 

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SCIENTISTS I'M GOING TO TALK 

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ABOUT MY OWN RESEARCH.  AND THE 

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NEXT STEP WHICH IS KIND OF, YOU 

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KNOW, ENCOURAGING RADIOLOGISTS 

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AND IMAGEERS TO CONTINUE ON WITH

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RESEARCH.  

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ESPECIALLY IN THIS CURRENT 

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ENVIRONMENT WHERE RADIOLOGIST 

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CONSIST GO OUT.  IT'S LUCRATIVE 

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TO MAKE MONEY. 

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YOU CAN READ IMAGES IN YOUR 

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BUNNY SLEEPERS IN YOUR BASEMENT 

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AND, YOU KNOW, MAKE HUNDREDS OF 

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THOUSANDS OF DOLLARS AND PEOPLE 

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WHO MIGHT OTHERWISE HAVE THE 

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DRIVE TO DO RESEARCH FEEL LIKE 

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MAYBE THEY'RE BEING LEFT OUT IF 

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THEY MAKE THIS CHOICE.  AND SO 

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SOME OF OUR TRAINING GRANTS THAT

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INVIGORATE RESEARCH AND TO 

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SUPPORT THE DESIRES OF OUR 

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RESIDENTS AND FELLOW WHO IS ARE 

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INTERESTED IN PURSUING RESEARCH 

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AND HELPING THEM ACHIEVE THEIR 

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DREAM. 

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BEFORE I BEGIN I JUST WANT TO 

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TALK ABOUT MY COLLABORATORS.  WE

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USUALLY PUT THESE SLIDES AT THE 

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END AND SOMETIMES EVERYBODY 

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STARTS ASKING QUESTIONS AND I 

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FORGET TO THANK THEM.  SO I WANT

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TO THANK THEM UP FRONT BECAUSE 

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THIS IS REALLY A MULTIMODALITY, 

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YOU KNOW, COMBINED APPROACH FOR 

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RESEARCH.  

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NOT JUST RADIOLOGY BUT WE HAVE 

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CARDIOLOGISTS HELPING US DO SITE

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SEEK TO HELP US UNDERSTAND SOME 

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OF THE TARGETS THAT WE'RE 

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IMAGING, PATHOLOGY AND 

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IMMUNOLOGY, WE HAVE PARTNERS AT 

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SEEDER SINAI WHERE WE'RE TRYING 

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TO DEMONSTRATE THAT NOT ONLY CAN

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WE TRANSLATE INTO HUMANS BUT WE 

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CAN TRANSLATE ACROSS THE DUN  

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COUNTRY SO YOU DON'T HAVE JUST 

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TO COME TO WASH U YOU CAN COME 

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ACROSS THE COUNTRY.  I WANT TO 

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HIGHLIGHT THE YANG LU LAB.  NOW 

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HE IS IS FULL PROFESSOR AND 

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WORKING WITH ME AND ALSO WITH 

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MICHAEL WELL VP AND IS NOW TAKEN

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UP THE MANTEL IN DEVELOPING SOME

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OF THESE NOVEL RADIO TRACERS 

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AND, YOU KNOW, COULDN'T BE 

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MOVING THIS FORWARD WITHOUT HIM.

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HIS GROUP IS THE ONE STILL RADIO

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LABELS OUR TRACER THE DAY BEFORE

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THE IMAGING SO WE INJECT AND 

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VERY IMPORTANT TO THE SUCCESS OF

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THIS RESEARCH AND THEN ALSO TO 

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THE CENTER FOR CLINICAL IMAGING 

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RESEARCH WHICH I LED INTO LAST 

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YEAR WHEN I BECAME CHAIR AND 

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THIS TEAM IS REALLY EXPERTS IN 

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GETTING THESE NOVEL TRACERS, 

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INJECTING THEM INTO PEOPLE AND 

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MAKING SURE THE EXAM MOVES 

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FORWARD.  SO I THINK WE CAN ALL 

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AGREE AND THE NIH HAS PROMOTED 

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THIS THAT PRECISION IMAGING IS 

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KEY TO BRINGING PRECISION 

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MEDICINE TO THE PATIENT.  AND 

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ONE OF THE KEYS IS MOLECULAR 

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IMAGING THE FACT THAT WE CANNOT 

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ONLY IMAGE AT THE ANATOMIC LEVEL

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BUT WE CAN IMAGE AT THE CELLULAR

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LEVEL AND EVEN THE SUB CELLULAR 

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LEVEL AND LEARN WHAT'S GOING ON 

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IN PATIENTS.  THROUGH MOLECULAR 

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IMAGING SO UNDERSTANDING THE 

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IMMUNOLOGY.  PARTICULARLY 

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THROUGH ARTERY ROW SCLEROSIS.  

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THERE WAS A POINT IN MY CAREER 

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WHERE I WAS INTERESTED IN 

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LOOKING AT A SPECIFIC RECEPTOR. 

252
00:10:44,458 --> 00:10:46,426
AND I WENT TO MIKE WELCH AND 

253
00:10:46,426 --> 00:10:50,630
SAID I WOULD LIKE TO MAKE AN MR 

254
00:10:50,630 --> 00:10:51,898
AGENT AND HE SAID WE STARTED 

255
00:10:51,898 --> 00:10:53,500
LOOKING AT THE RECEPTOR DENSITY 

256
00:10:53,500 --> 00:10:55,602
AND IT TURNED OUT WE DIDN'T HAVE

257
00:10:55,602 --> 00:10:57,604
ENOUGH SIGNAL TO SEE IT SO HE 

258
00:10:57,604 --> 00:11:00,707
SAID LET'S PUT COOPER 64 ON IT 

259
00:11:00,707 --> 00:11:04,211
AND THAT'S WHERE MY I SHOULD SAY

260
00:11:04,211 --> 00:11:06,580
MY VENTURE INTO PET BEGAN. 

261
00:11:06,580 --> 00:11:08,181
BECAUSE MY POSTDOC IF YOU WANT 

262
00:11:08,181 --> 00:11:09,716
TO SAY I DID A POSTDOC I WAS 

263
00:11:09,716 --> 00:11:12,185
HALF ATTENDING, HALF FELLOW WITH

264
00:11:12,185 --> 00:11:15,222
MARK WAS ALL MRI.  SO, YOU KNOW,

265
00:11:15,222 --> 00:11:21,061
WE STARTED LOOKING AT 

266
00:11:21,061 --> 00:11:21,495
ARTHROSCLEROSIS AND 

267
00:11:21,495 --> 00:11:22,429
ARTHROSCLEROSIS IS A SYSTEMIC 

268
00:11:22,429 --> 00:11:24,197
PROCESS OF INFLAMMATION, 

269
00:11:24,197 --> 00:11:26,700
RUPTURE, REPAIR, AND IN ORDER TO

270
00:11:26,700 --> 00:11:28,769
TREAT THESE PARENTS WITH 

271
00:11:28,769 --> 00:11:30,937
PRECISION MEDICINE UNDERSTANDING

272
00:11:30,937 --> 00:11:32,305
SPECIFIC -- PATIENT SPECIFIC 

273
00:11:32,305 --> 00:11:33,607
BIOMARKERS IS NEEDED AND SO, YOU

274
00:11:33,607 --> 00:11:35,075
KNOW, IT'S NOT JUST IMAGING BUT 

275
00:11:35,075 --> 00:11:37,644
ONCE WE UNDERSTAND WHAT SOME OF 

276
00:11:37,644 --> 00:11:40,447
THESE RECEPTORS ARE, CAN WE 

277
00:11:40,447 --> 00:11:42,449
MODIFY THE PHYSIOLOGIC PROCESS 

278
00:11:42,449 --> 00:11:43,950
THROUGH TARGETING RECEPTORS NOT 

279
00:11:43,950 --> 00:11:47,187
JUST WITH IMAGING BUT ALSO WITH 

280
00:11:47,187 --> 00:11:49,656
THERAPEUTICS.  AND SO, YOU KNOW,

281
00:11:49,656 --> 00:11:53,126
ONE OF THE QUESTIONS MIGHT BE 

282
00:11:53,126 --> 00:11:55,428
WHY DO WE CARE?  I DON'T KNOW 

283
00:11:55,428 --> 00:11:57,631
HOW MANY OF YOU, SOME OF YOU ARE

284
00:11:57,631 --> 00:12:00,433
OLD ENOUGH TO REMEMBER WHO THIS 

285
00:12:00,433 --> 00:12:04,971
MAN IS.  AND THIS IS TIM R. WITH

286
00:12:04,971 --> 00:12:06,540
MEET THE PRESS AND I REMEMBER, I

287
00:12:06,540 --> 00:12:09,476
WAS ACTUALLY ON VACATION ON CAPE

288
00:12:09,476 --> 00:12:12,412
COD AND HAVING DINNER WITH MY 

289
00:12:12,412 --> 00:12:13,647
HUSBAND AND TIM ARE YOUS CERT 

290
00:12:13,647 --> 00:12:15,015
WAS SUPPOSED TO DO THE NEWS AND 

291
00:12:15,015 --> 00:12:16,817
INSTEAD SOMEBODY ELSE CAME ON 

292
00:12:16,817 --> 00:12:19,953
AND SAID, EXCUSE ME, SAID THAT 

293
00:12:19,953 --> 00:12:21,655
HI HAD PASSED AWAY AND WOULD NOT

294
00:12:21,655 --> 00:12:25,425
BE DOING THE NEWS THAT NIGHT. 

295
00:12:25,425 --> 00:12:27,594
AND WHAT WAS SHOCKING WAS THAT 

296
00:12:27,594 --> 00:12:29,563
HE HAD PREVIOUSLY HAD A STRESS 

297
00:12:29,563 --> 00:12:31,198
TEST JUST LIKE ABOUT MONTH 

298
00:12:31,198 --> 00:12:31,965
EARLIER, A MONTH AND A HALF 

299
00:12:31,965 --> 00:12:34,935
EARLIER WITH NORMAL RESULTS.  HE

300
00:12:34,935 --> 00:12:39,940
HAD NO SIGNS OF ISCHEMIA, HE WAS

301
00:12:39,940 --> 00:12:41,641
SIGNED YOU HAVE AS BEING HEALTHY

302
00:12:41,641 --> 00:12:45,846
AND HE WAS ASYMPTOMATIC.  SO ONE

303
00:12:45,846 --> 00:12:51,418
OF THE, THIS IS SORT OF AN 

304
00:12:51,418 --> 00:12:52,953
OBVIOUS INCIDENT THAT HIGHLIGHTS

305
00:12:52,953 --> 00:12:55,355
THAT NEARLY ONE-HALF OF PATIENTS

306
00:12:55,355 --> 00:12:57,757
WITH SUDDEN DEATH OR STROKES ARE

307
00:12:57,757 --> 00:12:58,992
ASYMPTOMATIC PATIENTS AND DIE 

308
00:12:58,992 --> 00:13:00,794
FROM LESIONS THAT AREN'T FLOW 

309
00:13:00,794 --> 00:13:02,796
LIMITING.  THAT RUPTURE AND THEY

310
00:13:02,796 --> 00:13:06,833
CAUSE MI OR STROKE.  SO ONE 

311
00:13:06,833 --> 00:13:09,135
QUESTION IS, HOW DO WE IDENTIFY 

312
00:13:09,135 --> 00:13:12,038
THESE PATIENTS AND JUST ON A 

313
00:13:12,038 --> 00:13:14,241
VERY BASIC LEVEL, THERE ARE TWO 

314
00:13:14,241 --> 00:13:16,743
ARTERY ROW SLER ROTTIC TYPES OF 

315
00:13:16,743 --> 00:13:17,043
LEGIONS. 

316
00:13:17,043 --> 00:13:19,346
AND THIS IS VERY SIMPLISTIC.  

317
00:13:19,346 --> 00:13:20,847
THERE ARE THOSE THAT ARE STEN 

318
00:13:20,847 --> 00:13:22,449
NOTTIC AND THOSE THAT ARE NOT 

319
00:13:22,449 --> 00:13:25,285
STEN NOTTIC.  AND THE STEN 

320
00:13:25,285 --> 00:13:29,089
NOTTIC ONES ARE FEW, THEY MAY BE

321
00:13:29,089 --> 00:13:29,389
CALCIFIED. 

322
00:13:29,389 --> 00:13:31,024
THEY MAY CAUSE ANGIE KNOW WHEN 

323
00:13:31,024 --> 00:13:33,193
YOU WALK TO THE MAILBOX BUT NOT 

324
00:13:33,193 --> 00:13:34,928
THE ONES THAT ARE GOING TO 

325
00:13:34,928 --> 00:13:36,796
RUPTURE AND KILL YOU THE ONES 

326
00:13:36,796 --> 00:13:38,965
THAT WILL KILL YOU AND GIVE YOU 

327
00:13:38,965 --> 00:13:40,934
A MYOCARDIAL INFARCTION ARE THE 

328
00:13:40,934 --> 00:13:42,936
ONES THAT ARE NOT STABLE.  THEY 

329
00:13:42,936 --> 00:13:44,471
ARE LIPID RICH, THEY ARE 

330
00:13:44,471 --> 00:13:45,672
INFLAMED AND THEY MAY LOOK LIKE 

331
00:13:45,672 --> 00:13:50,343
THIS.  SO THIS IS A PATIENT WITH

332
00:13:50,343 --> 00:13:53,647
TWO LESIONS AND THE FIRST IS A 

333
00:13:53,647 --> 00:13:55,782
VERY STABLE CALCIFIED LESION YOU

334
00:13:55,782 --> 00:13:57,784
KNOW AT THE JUNCTION OF THE LEFT

335
00:13:57,784 --> 00:14:01,655
MAIN AND LAD BUT THE SECOND W IS

336
00:14:01,655 --> 00:14:03,690
THIS PLAQUE WHERE THERE'S NO 

337
00:14:03,690 --> 00:14:05,358
CALCIUM, YOU CAN SEE THERE'S A 

338
00:14:05,358 --> 00:14:08,295
LOT OF SOFT TISSUE, A LOT OF 

339
00:14:08,295 --> 00:14:10,030
NON-CALCIUM FEWED PLAQUE AND IF 

340
00:14:10,030 --> 00:14:12,832
YOU LOOK AT THE TRANSVERSE 

341
00:14:12,832 --> 00:14:13,633
IMAGE. 

342
00:14:13,633 --> 00:14:15,135
LIKE RIGHT THROUGH HERE, THIS 

343
00:14:15,135 --> 00:14:17,737
BLUE BOX MATCHES THIS BLUE LINE,

344
00:14:17,737 --> 00:14:21,641
YOU CAN SEE THAT THIS IS PLAQUE 

345
00:14:21,641 --> 00:14:23,843
THAT HAS RUPTURED THE LUMEN IS 

346
00:14:23,843 --> 00:14:25,645
VERY SMALL.  HERE IT LOOKS 

347
00:14:25,645 --> 00:14:27,080
COMPLETELY GONE AND THIS IS THE 

348
00:14:27,080 --> 00:14:28,982
ONE THAT IS THE CULPRIT LESION 

349
00:14:28,982 --> 00:14:32,419
THAT IS GIVEN THE PATIENT AN 

350
00:14:32,419 --> 00:14:36,589
EVENT.  SO WHEN WE LOOK AT 

351
00:14:36,589 --> 00:14:38,024
HISTOPATHOLOGY AND REASONS FOR 

352
00:14:38,024 --> 00:14:40,460
PLAQUE AND STABILITY, WE LOOK 

353
00:14:40,460 --> 00:14:42,128
FOR INFILTRATION WITH 

354
00:14:42,128 --> 00:14:45,665
MACROPHAGES, WE LOOK FOR LARGE 

355
00:14:45,665 --> 00:14:50,537
LIPID NECROTIC CORE AND THIN 

356
00:14:50,537 --> 00:14:50,870
FI

357
00:14:50,870 --> 00:14:51,905
FIBROUS CAP AND THESE ARE 

358
00:14:51,905 --> 00:14:53,640
WELL-KNOWN FEATURES.  ANYONE 

359
00:14:53,640 --> 00:14:57,177
THAT LOOKS AT ARTERY ROW 

360
00:14:57,177 --> 00:14:59,212
SCLEROSIS KNOWS THESE.  I AM 

361
00:14:59,212 --> 00:15:01,348
GOING TO FOCUS ON THREE CELL 

362
00:15:01,348 --> 00:15:01,648
TYPES. 

363
00:15:01,648 --> 00:15:06,987
THERE'S THE MACROPHAGES AND THE 

364
00:15:06,987 --> 00:15:07,320
MO

365
00:15:07,320 --> 00:15:08,455
MONOCYTES AND THERE ARE ALSO 

366
00:15:08,455 --> 00:15:09,522
SMOOTH MUSCLE CELLS AND WHAT'S 

367
00:15:09,522 --> 00:15:11,558
VERY INTERESTING IS THAT THE 

368
00:15:11,558 --> 00:15:15,228
SMOOTH MUSCLE CELLS START TO 

369
00:15:15,228 --> 00:15:18,131
MIGRATE THROUGH THE, YOU KNOW, 

370
00:15:18,131 --> 00:15:21,267
THROUGH THE INTIMA UP TO THE 

371
00:15:21,267 --> 00:15:22,702
SURFACE AND IF YOU'VE TALKED TO 

372
00:15:22,702 --> 00:15:24,537
A FEW FOLKS, I DON'T KNOW HOW 

373
00:15:24,537 --> 00:15:28,308
MANY OF YOU KNOW GARY OWENS BUT 

374
00:15:28,308 --> 00:15:30,677
HE'S AT THE UNIVERSITY OF 

375
00:15:30,677 --> 00:15:32,679
VIRGINIA AND IS A VASCULAR 

376
00:15:32,679 --> 00:15:34,447
BIOLOGIST AND ONE OF THE THINGS,

377
00:15:34,447 --> 00:15:36,349
HE AND I HAVE HAD A LOT OF 

378
00:15:36,349 --> 00:15:38,518
DISCUSSION ABOUT THE RECEPTORS 

379
00:15:38,518 --> 00:15:40,453
THAT WE END UP SEEING ON ALL 

380
00:15:40,453 --> 00:15:44,891
THREE CELL TYPES IS THAT THERE'S

381
00:15:44,891 --> 00:15:48,261
VASCULAR CELL MIGRATION AND WITH

382
00:15:48,261 --> 00:15:50,063
THAT, SEVERAL ARTICLES BELIEVE 

383
00:15:50,063 --> 00:15:51,464
THAT THERE'S PHENOTYPE CHANGE 

384
00:15:51,464 --> 00:15:54,000
AND SO YOU HAVE VASCULAR SMOOTH 

385
00:15:54,000 --> 00:15:56,302
MUSCLE CELLS THAT BECOME 

386
00:15:56,302 --> 00:15:57,904
MACROPHAGE-LIKE AND A FEW THAT 

387
00:15:57,904 --> 00:16:00,173
MIGRATE UP TO THE SURFACE AND 

388
00:16:00,173 --> 00:16:01,674
BECOME LIKE ENDOTHELIAL CELLS.  

389
00:16:01,674 --> 00:16:04,878
THERE'S ONE RECEPTOR, THE 

390
00:16:04,878 --> 00:16:07,881
PEPTIDE RECEPTOR THAT WE'VE BEEN

391
00:16:07,881 --> 00:16:11,217
IMAGING THAT WE SEE MOSTLY IN 

392
00:16:11,217 --> 00:16:13,286
THE DEEP INTIMA ON MACROPHAGES 

393
00:16:13,286 --> 00:16:15,021
BUT WE ALSO SEE IN SOME OF THE 

394
00:16:15,021 --> 00:16:16,456
SMOOTH MUSCLE CELLS AND ALSO SEE

395
00:16:16,456 --> 00:16:18,958
IN A FEW OF THE ENDOTHELIAL 

396
00:16:18,958 --> 00:16:20,393
CELLS AND SO I'M GOING TO TALK A

397
00:16:20,393 --> 00:16:22,028
LITTLE BIT ABOUT THAT RECEPTOR 

398
00:16:22,028 --> 00:16:23,930
WHEN WE STARTED IMAGING THIS, 

399
00:16:23,930 --> 00:16:25,665
YOU KNOW, ALL WE KNOW WAS 

400
00:16:25,665 --> 00:16:31,971
THAT -- WE KNEW IT WAS ON 

401
00:16:31,971 --> 00:16:35,809
MACROPHAGES AND WE ALSO SEE IT 

402
00:16:35,809 --> 00:16:38,211
ON SOME OF THE HISTOCHEMISTRY IN

403
00:16:38,211 --> 00:16:40,447
THE VASCULAR SMOOTH MUSCLE CELLS

404
00:16:40,447 --> 00:16:43,183
AND A FEW IN THE ENDOTHELIAL 

405
00:16:43,183 --> 00:16:45,518
CELLS, WHAT'S GOING ON HERE?  

406
00:16:45,518 --> 00:16:50,790
THERE'S -- LINCOLN POTTER IS A 

407
00:16:50,790 --> 00:16:54,861
PEPTIDE EXPERT.  AND WHEN WE 

408
00:16:54,861 --> 00:16:57,664
TALK ABOUT PEPTIDES, B, WITH 

409
00:16:57,664 --> 00:17:02,469
HEART FAILURE, PEPTIDE C IS 

410
00:17:02,469 --> 00:17:04,237
RESPONSIBLE FOR THE STATUS.  

411
00:17:04,237 --> 00:17:06,372
THAT'S HOW THE SNAKE KILLS YOU 

412
00:17:06,372 --> 00:17:10,376
BY GIVING YOU CMP AND CAUSING 

413
00:17:10,376 --> 00:17:12,946
YOU TO VASODILATE AND YOU DIE.  

414
00:17:12,946 --> 00:17:14,747
BUT WHAT WAS VERY INTERESTING 

415
00:17:14,747 --> 00:17:17,650
WAS I ASKED HIM, I SAID, WHY -- 

416
00:17:17,650 --> 00:17:23,223
WHAT IS -- THIS IS WHERE YOU 

417
00:17:23,223 --> 00:17:26,926
HAVE SMOOTH MUSCLE CELLS.  WHAT 

418
00:17:26,926 --> 00:17:29,395
IS IT DOING?  THIS WAS WAY BACK 

419
00:17:29,395 --> 00:17:34,367
IN 2003-04.  HE SAID PAM, GOD 

420
00:17:34,367 --> 00:17:36,202
PUT IT THERE FOR YOU TO IMAGE.  

421
00:17:36,202 --> 00:17:38,938
I'M SITTING THERE GOING, WELL, 

422
00:17:38,938 --> 00:17:39,939
FIRST OF ALL, GOD, HE'S THINKING

423
00:17:39,939 --> 00:17:41,808
ABOUT MY RESEARCH CAREER.  YOU 

424
00:17:41,808 --> 00:17:45,145
KNOW, I'M SITTING THERE GOING 

425
00:17:45,145 --> 00:17:46,045
THAT DOESN'T QUITE MAKE SENSE.  

426
00:17:46,045 --> 00:17:48,648
BUT THERE ARE A LOT OF DIFFERENT

427
00:17:48,648 --> 00:17:51,651
TARGETS THAT PEOPLE HAVE IMAGED 

428
00:17:51,651 --> 00:17:53,019
IN ARTHROSCLEROSIS, AND REALLY 

429
00:17:53,019 --> 00:17:56,089
THIS IS A MICROCOSM OF COMPLEX 

430
00:17:56,089 --> 00:17:58,191
ACTIVITY, YOU KNOW, THERE ARE 

431
00:17:58,191 --> 00:18:00,927
VASCULAR ADHESION MODULES, THERE

432
00:18:00,927 --> 00:18:02,295
ARE CHEMOKINES AND WE ARE 

433
00:18:02,295 --> 00:18:05,465
IMAGING A LOT OF THIS IN OUR 

434
00:18:05,465 --> 00:18:06,266
LABORATORIES AT WASHINGTON 

435
00:18:06,266 --> 00:18:11,104
UNIVERSITY CC R 2, THERE'S AN MP

436
00:18:11,104 --> 00:18:14,807
I'M ON WITH LEE YOU AND THERE 

437
00:18:14,807 --> 00:18:16,509
ARE MMPS A NUMBER OF FOLKS ARE 

438
00:18:16,509 --> 00:18:21,181
LOOKING AT THIS, MMPS IN IN 

439
00:18:21,181 --> 00:18:21,481
ANEURYSMS.  

440
00:18:21,481 --> 00:18:26,219
ALPHA V BETA 3, PEOPLE LOOK AT 

441
00:18:26,219 --> 00:18:29,689
ANGIOGENESIS.  AND ALPHA V BETA 

442
00:18:29,689 --> 00:18:31,624
3 AND ENDOTHELIAL CELLS AND 

443
00:18:31,624 --> 00:18:34,861
PEOPLE HAVE ALSO LOOKED AT 

444
00:18:34,861 --> 00:18:37,630
HYPOXIC PLAQUE.  THERE ARE RADIO

445
00:18:37,630 --> 00:18:39,332
TRACERS THAT LOOK AT PLAQUE 

446
00:18:39,332 --> 00:18:42,569
HYPOXIA OR CELLS AND WE HAVE 

447
00:18:42,569 --> 00:18:47,674
USED THEM LIKE WE CAN LOOK AT 

448
00:18:47,674 --> 00:18:51,010
TUMORS.  I THINK PETER, YOU'RE 

449
00:18:51,010 --> 00:18:52,512
PROBABLY FAMILIAR WITH PEOPLE 

450
00:18:52,512 --> 00:18:56,749
LOOKING AT HYPOXIC CELLS IN 

451
00:18:56,749 --> 00:18:58,484
TUMORS BUT WE'VE BEEN ABLE TO 

452
00:18:58,484 --> 00:19:02,021
SEE HYPOXIC CELLS IN 

453
00:19:02,021 --> 00:19:02,855
ARTHROSCLEROSIS USING SOME OF 

454
00:19:02,855 --> 00:19:04,090
THE SAME AGENTS AND THEN OF 

455
00:19:04,090 --> 00:19:09,662
COURSE THERE'S THIS TARGET, THE 

456
00:19:09,662 --> 00:19:11,097
NATRIUR

457
00:19:11,097 --> 00:19:15,702
NATRIURETIC C THAT HAVE GOTTEN 

458
00:19:15,702 --> 00:19:17,537
INTO HUMANS.  SO AWHILE AGO 

459
00:19:17,537 --> 00:19:19,372
THERE WAS A GRANT, THE PROGRAM 

460
00:19:19,372 --> 00:19:22,575
OF EXCELLENCE IN NAN TECHNOLOGY 

461
00:19:22,575 --> 00:19:26,346
THAT ELLIE PIONEERED WHEN HE WAS

462
00:19:26,346 --> 00:19:31,851
THE DIRECTOR OF THE NIH AND WE 

463
00:19:31,851 --> 00:19:33,519
WERE FORTUNATE ENOUGH TO HAVE 

464
00:19:33,519 --> 00:19:34,487
ONE OF THOSE GRANTS AND THE 

465
00:19:34,487 --> 00:19:38,291
AGENT THAT WE GOT INTO HUMAN 

466
00:19:38,291 --> 00:19:41,928
SUBJECTS WAS THE RADIO TRACER 

467
00:19:41,928 --> 00:19:45,365
THAT TARGETED MPRC AND IT WAS 

468
00:19:45,365 --> 00:19:46,499
FUNDED THROUGH THAT GRANT AND IT

469
00:19:46,499 --> 00:19:50,103
WAS THE PROGRAM OF EXCELLENCE IN

470
00:19:50,103 --> 00:19:51,137
NANOTECHNOLOGY WE STARTED TO 

471
00:19:51,137 --> 00:19:55,208
LOOK AT NANO IMAGING USING THIS 

472
00:19:55,208 --> 00:19:56,976
PEPTIDE AND ONE QUESTION WAS, 

473
00:19:56,976 --> 00:19:58,311
YOU KNOW, BEYOND JUST DIAGNOSIS.

474
00:19:58,311 --> 00:20:00,413
CAN THESE AGENTS PREDICT 

475
00:20:00,413 --> 00:20:02,415
OUTCOME?  CAN THEY INCREASE OUR 

476
00:20:02,415 --> 00:20:04,484
UNDERSTANDING OF MECHANISM?  AND

477
00:20:04,484 --> 00:20:07,520
THEN REALLY THE HOLY GRAIL IS 

478
00:20:07,520 --> 00:20:09,822
CAN WE USE THEM ALSO FOR 

479
00:20:09,822 --> 00:20:13,326
THERAPY?  AND I MENTIONED THE 

480
00:20:13,326 --> 00:20:15,461
MULTIPLE DIFFERENT TARGETS THAT 

481
00:20:15,461 --> 00:20:17,630
COULD BE USED.  FOR THESE RADIO 

482
00:20:17,630 --> 00:20:20,466
TRACERS OR FUNCTIONALIZED 

483
00:20:20,466 --> 00:20:23,036
NANOPARTICLES AND CERTAINLY WITH

484
00:20:23,036 --> 00:20:24,337
ARTHROSCLEROSIS A LOT THAT ARE 

485
00:20:24,337 --> 00:20:27,840
PRESENT ON MACROPHAGES OR 

486
00:20:27,840 --> 00:20:30,443
MONOCYTES WE HAVE A RADIO TRACER

487
00:20:30,443 --> 00:20:32,545
THAT TARGETS KETO CAME RECEPTOR,

488
00:20:32,545 --> 00:20:40,053
PEOPLE HAVE LOOKED AT CD 68.  

489
00:20:40,053 --> 00:20:41,888
P32.  ACTIVATED CELLS.  AND 

490
00:20:41,888 --> 00:20:43,656
HYPOXIA AND MPRC THAT WE'RE 

491
00:20:43,656 --> 00:20:45,258
LOOKING AT AND THEN, YOU KNOW, 

492
00:20:45,258 --> 00:20:47,327
MANY PEOPLE HAVE LOOKED AT 

493
00:20:47,327 --> 00:20:51,297
ENDOTHELIAL CELLS LIKE VEGF AND 

494
00:20:51,297 --> 00:20:53,099
THE INTE GRANTS.  AND SO, YOU 

495
00:20:53,099 --> 00:20:55,835
KNOW, WHEN WE TALK ABOUT IMAGING

496
00:20:55,835 --> 00:20:57,503
AGENTS PEOPLE TALK ABOUT SMALL 

497
00:20:57,503 --> 00:20:59,005
MOLECULES VERSUS PROTEINS VERSUS

498
00:20:59,005 --> 00:21:02,909
NAN PARTICLES AND THE SMALL 

499
00:21:02,909 --> 00:21:04,977
MOLECULES ARE REALLY THE MOST 

500
00:21:04,977 --> 00:21:05,211
COMMON. 

501
00:21:05,211 --> 00:21:07,580
THESE ARE AGENTS BELOW TWO 

502
00:21:07,580 --> 00:21:11,351
THOUSAND KILO DALTONS.  AND LESS

503
00:21:11,351 --> 00:21:16,122
THAN -- THAN ONE NANO MOLE BUT 

504
00:21:16,122 --> 00:21:17,256
FDG FOR INSTANCE IS ONE OF THE 

505
00:21:17,256 --> 00:21:19,425
MOST COMMON THAT WE USE AND 

506
00:21:19,425 --> 00:21:23,463
THAT'S FOR PET. 

507
00:21:23,463 --> 00:21:27,867
ION CONTRAST FOR CT AND THEN 

508
00:21:27,867 --> 00:21:30,636
PROTEINS, WE HAVE RADIO LABELED 

509
00:21:30,636 --> 00:21:32,905
MONOCLONAL ANTIBODIES THEY CAN 

510
00:21:32,905 --> 00:21:33,639
OFFER PRECISE INFORMATION AND 

511
00:21:33,639 --> 00:21:37,276
THEN NANOPARTICLES.  NOW 

512
00:21:37,276 --> 00:21:38,144
NANOPARTICLES ARE VERY SMALL AND

513
00:21:38,144 --> 00:21:40,146
ONE OF THE NICE THINGS ABOUT 

514
00:21:40,146 --> 00:21:42,348
THEM TOO IS THAT WE'VE 

515
00:21:42,348 --> 00:21:45,351
DISCOVERED THAT WHEN YOU USE 

516
00:21:45,351 --> 00:21:47,553
THEM, YOU COULD CONCEIVABLY 

517
00:21:47,553 --> 00:21:49,655
INJECT LESS THAN 100 MICRO GRAMS

518
00:21:49,655 --> 00:21:51,657
INTO THE HUMAN SUBJECT. 

519
00:21:51,657 --> 00:21:54,761
AND SO COULD QUALIFY FOR AN EIND

520
00:21:54,761 --> 00:21:57,630
SO REALLY EASILY TRANSLATED INTO

521
00:21:57,630 --> 00:22:00,366
HUMAN SUBJECTS OR AT LEAST NOW 

522
00:22:00,366 --> 00:22:01,401
EASILY TRANSLATE TO THE TIME 

523
00:22:01,401 --> 00:22:03,102
WHEN WE FIRST STARTED DOING THIS

524
00:22:03,102 --> 00:22:05,638
WE WERE CONCERNED THAT THE FDA 

525
00:22:05,638 --> 00:22:09,675
WOULD NOT WANT TO APPROVE A 

526
00:22:09,675 --> 00:22:10,510
NANOPARTICLE FOR INJECTION INTO 

527
00:22:10,510 --> 00:22:12,111
A HUMAN SUBJECT. 

528
00:22:12,111 --> 00:22:14,680
THAT WASN'T, YOU KNOW, THAT 

529
00:22:14,680 --> 00:22:17,417
WOULD CONTINUE TO LIVE.  I THINK

530
00:22:17,417 --> 00:22:18,951
THERE HAVE BEEN A FEW THAT HAD 

531
00:22:18,951 --> 00:22:23,322
BEEN EIN -- OR INDS HAD BEEN 

532
00:22:23,322 --> 00:22:24,724
APPROVED FOR PATIENTS WHO WERE 

533
00:22:24,724 --> 00:22:28,094
TERMINAL.  SO MOST OF YOU ARE 

534
00:22:28,094 --> 00:22:29,095
FAMILIAR WITH THE SMALL 

535
00:22:29,095 --> 00:22:34,300
MOLECULES LIKE THE NANOPARTICLES

536
00:22:34,300 --> 00:22:37,470
AND ALSO NANOPARTICLES THAT ARE 

537
00:22:37,470 --> 00:22:40,406
CURRENTLY USED IN HUMAN 

538
00:22:40,406 --> 00:22:42,408
ARTHROSCLEROSIS SO LIKE FARRAH A

539
00:22:42,408 --> 00:22:45,044
HOME ANOTHER US PIOS AND THESE 

540
00:22:45,044 --> 00:22:48,147
IRON BASED AGENCIES ARE COMMONLY

541
00:22:48,147 --> 00:22:49,615
USED, HAVE HAD A LONG HISTORY 

542
00:22:49,615 --> 00:22:52,785
WHERE YOU INJECT AND THEN THEY 

543
00:22:52,785 --> 00:22:54,887
ARE TAKEN UP BY MACROPHAGES AND 

544
00:22:54,887 --> 00:22:57,156
THEY START TO MAKE THE PLAQUE. 

545
00:22:57,156 --> 00:22:57,990
LOOK DARK AND YOU CAN SEE THIS 

546
00:22:57,990 --> 00:23:02,094
IS A PATIENT, THIS IS NOT MY 

547
00:23:02,094 --> 00:23:03,129
RESEARCH, IT'S FROM THE 

548
00:23:03,129 --> 00:23:05,465
LITERATURE.  BUT YOU CAN SEE 

549
00:23:05,465 --> 00:23:09,635
THAT THE -- THIS IS WITH NO 

550
00:23:09,635 --> 00:23:12,238
THERAPY.  IT IS TAKEN UP AND THE

551
00:23:12,238 --> 00:23:14,006
PLAQUE STARTS TO BECOME DARK AND

552
00:23:14,006 --> 00:23:15,875
AS YOU START TO TREAT THIS 

553
00:23:15,875 --> 00:23:18,845
PATIENT THIS PATIENT IS BEING 

554
00:23:18,845 --> 00:23:20,279
TREATED WITH ATORVASTATIN AND 

555
00:23:20,279 --> 00:23:25,651
THIS GRADUALLY DECREASES AND 

556
00:23:25,651 --> 00:23:28,521
MAPS HAVE BEEN USED TO KIND OF 

557
00:23:28,521 --> 00:23:32,892
HIGHLIGHT THE CHANGE.  SO, FDG 

558
00:23:32,892 --> 00:23:35,461
AS WELL, IS ANOTHER AGENT.  AND 

559
00:23:35,461 --> 00:23:38,598
EVERYBODY'S FAMILIAR WITH FDG, 

560
00:23:38,598 --> 00:23:40,533
IT'S A GLUCOSE ANALOG AND THERE 

561
00:23:40,533 --> 00:23:45,371
YOU'RE ESSENTIALLY LOOKING AT 

562
00:23:45,371 --> 00:23:45,905
METABOLIC ACTIVITY.  SO 

563
00:23:45,905 --> 00:23:48,207
IDENTIFIES METABOLLICALLY ACTIVE

564
00:23:48,207 --> 00:23:51,310
CAROTID PLAQUE BUT NECESSARILY 

565
00:23:51,310 --> 00:23:54,146
DOESN'T REALLY TELL YOU EXACTLY 

566
00:23:54,146 --> 00:23:56,482
WHY.  SO, SOME OF THE PET 

567
00:23:56,482 --> 00:23:58,417
TRACERS THAT TARGET SPECIFIC 

568
00:23:58,417 --> 00:23:59,118
RECEPTORS AND CELLS THAT CAN BE 

569
00:23:59,118 --> 00:24:02,889
USED IN HUMAN SUBJECTS ARE THIS 

570
00:24:02,889 --> 00:24:05,691
COPPER 64 CNF AND THIS HAS BEEN 

571
00:24:05,691 --> 00:24:09,061
NIH FUNDED NOW STARTING BACK, IT

572
00:24:09,061 --> 00:24:15,801
WAS BACK IN 2010-11 WITH THE PEN

573
00:24:15,801 --> 00:24:18,838
GRANT AND WE'RE NOW IN OUR 

574
00:24:18,838 --> 00:24:21,140
SECOND CYCLE OF COMPETITIVE 

575
00:24:21,140 --> 00:24:23,509
FUNDING WITH AN RO 1.  I SHOULD 

576
00:24:23,509 --> 00:24:27,713
SAY, SO WE'VE HAD TWO RO 1S 

577
00:24:27,713 --> 00:24:30,683
SINCE THE PEN GRANT AND THIS 

578
00:24:30,683 --> 00:24:33,452
TARGETS THE RECEPTOR IN DEEP 

579
00:24:33,452 --> 00:24:35,054
MACROPHAGES AND THE VASCULAR 

580
00:24:35,054 --> 00:24:36,989
SMOOTH MUSCLE CELLS WE'VE ALSO 

581
00:24:36,989 --> 00:24:41,227
LOOKED AT COPPER ATSM AND 

582
00:24:41,227 --> 00:24:44,297
HYPOXIC PLAQUE AND YAWNING GIN 

583
00:24:44,297 --> 00:24:46,499
LOU HAS DEVELOPED AN AGENT IN 

584
00:24:46,499 --> 00:24:49,669
MONOCYTES.  SO IT'S REALLY A 

585
00:24:49,669 --> 00:24:51,637
TARGETING MONOCYTES AND I WILL 

586
00:24:51,637 --> 00:24:52,772
SHOW YOU SOME INTERESTING WORK 

587
00:24:52,772 --> 00:24:54,607
THAT'S BEEN DONE WITH THAT. 

588
00:24:54,607 --> 00:24:57,643
AND THERE ARE OTHER COMMON 

589
00:24:57,643 --> 00:24:59,612
AGENCI

590
00:24:59,612 --> 00:25:01,647
AGENCY -- AGENTS THAT PEOPLE 

591
00:25:01,647 --> 00:25:04,350
HAVE USED. 

592
00:25:04,350 --> 00:25:08,087
ONE IS SODIUM FLUORIDE AND THIS 

593
00:25:08,087 --> 00:25:09,689
IS AN AGENT THAT PEOPLE HAVE 

594
00:25:09,689 --> 00:25:11,924
USED MORE BONE IMAGING AND FOR 

595
00:25:11,924 --> 00:25:14,026
PROSTATE, TO ASSESS PROSTATE 

596
00:25:14,026 --> 00:25:15,394
MEDICINE BUT IT HAS BEEN SHOWN 

597
00:25:15,394 --> 00:25:17,830
TO BE A MARKER OF PLAQUE RUPTURE

598
00:25:17,830 --> 00:25:21,634
AND ACTIVE CALCIFICATION AND 

599
00:25:21,634 --> 00:25:26,339
POSITIVE REMODELLING.  F 18 GA 

600
00:25:26,339 --> 00:25:28,174
LACK TO RDG THAT IS ANOTHER 

601
00:25:28,174 --> 00:25:30,376
AGENT THAT IS AVAILABLE FOR 

602
00:25:30,376 --> 00:25:33,646
HUMANS.  HUMAN SUGGESTS.  

603
00:25:33,646 --> 00:25:37,617
TARGETS ALPHA BETA 3 AND THEN 

604
00:25:37,617 --> 00:25:44,256
GAL YUM, IT TARGETS THE 

605
00:25:44,256 --> 00:25:45,625
SOMATOSTATIN RECEPTOR IN 

606
00:25:45,625 --> 00:25:48,127
PROINFLAMMATORY MACROPHAGES AND 

607
00:25:48,127 --> 00:25:48,995
ONE OF THE INTERESTING THINGS 

608
00:25:48,995 --> 00:25:51,063
ABOUT THAT IS IT WAS DESIGNED 

609
00:25:51,063 --> 00:25:53,633
FOR ASSESSING ENDOCRINE TUMORS 

610
00:25:53,633 --> 00:25:56,469
AND WAS CO-OPTED.  SO A COUPLE 

611
00:25:56,469 --> 00:25:58,237
OF THESE THINGS WERE DESIGNED 

612
00:25:58,237 --> 00:26:00,473
FOR TUMOR IMAGING AND HAVE KIND 

613
00:26:00,473 --> 00:26:03,709
OF BEEN CO-OPTED TO LOOK AT 

614
00:26:03,709 --> 00:26:04,810
ARTHROSCLEROSIS, YOU KNOW, MOVED

615
00:26:04,810 --> 00:26:06,979
FOR OTHER USES.  AND THIS IS A 

616
00:26:06,979 --> 00:26:11,050
SLIDE FROM THE FOLKS AT EMBER 

617
00:26:11,050 --> 00:26:15,021
WHO HAVE BEEN -- HAD PIONEERED 

618
00:26:15,021 --> 00:26:17,156
THIS F 18 SODIUM FLUORIDE.  THIS

619
00:26:17,156 --> 00:26:24,964
IS F DASDA BUT NOT FOR THIS.  

620
00:26:24,964 --> 00:26:25,898
THERE'S A LESION RIGHT HERE AND 

621
00:26:25,898 --> 00:26:29,635
IF YOU HOOK AT CT, THIS IS A CT 

622
00:26:29,635 --> 00:26:34,473
CORONARY CTA, PET CT WITH THIS 

623
00:26:34,473 --> 00:26:38,844
AGENT AND THIS -- YOU CAN SEE 

624
00:26:38,844 --> 00:26:41,113
WHERE'S THERE A CULPRIT LESION 

625
00:26:41,113 --> 00:26:43,315
SO IT TAKES UP THE CULPRIT 

626
00:26:43,315 --> 00:26:44,850
LESION AND THEY LOOKED AT SOME 

627
00:26:44,850 --> 00:26:49,055
PATIENTS AND NOTED THAT THE 

628
00:26:49,055 --> 00:26:51,123
HIGHEST UPTAKE WAS SEEN IN THESE

629
00:26:51,123 --> 00:26:54,393
PATIENTS SO AS THE -- AS THE 

630
00:26:54,393 --> 00:26:55,695
PLAQUE HAS RUPTURED AND IS 

631
00:26:55,695 --> 00:26:57,430
STARTING TO LAY DOWN NEW BONE OR

632
00:26:57,430 --> 00:27:04,503
HYDROXY APPETITE.  SO, GAL YUM 

633
00:27:04,503 --> 00:27:06,639
68 IS VERY INTERESTING BECAUSE 

634
00:27:06,639 --> 00:27:08,374
IT WAS FDA APPROVED FOR 

635
00:27:08,374 --> 00:27:16,549
NEUROENDOCRINE TUMORS AND 

636
00:27:16,549 --> 00:27:20,086
TARGETS THE SOMATOSTATIN.  AND 

637
00:27:20,086 --> 00:27:21,654
IN ORDER TO LOOK AT THE 

638
00:27:21,654 --> 00:27:23,322
INFLAMMATION IN THE CORONARY 

639
00:27:23,322 --> 00:27:25,691
ARTERY YOU HAVE TO SUPPRESS ALL 

640
00:27:25,691 --> 00:27:28,027
THE MET BOLLIC ACTIVITY IN THE 

641
00:27:28,027 --> 00:27:31,397
HEART YOU HAVE TO PUT PATIENTS 

642
00:27:31,397 --> 00:27:32,998
ON SPECIAL DIETS AND IF YOU 

643
00:27:32,998 --> 00:27:35,568
CAN'T GET THE MYOCARDIUM 

644
00:27:35,568 --> 00:27:36,936
SUPPRESSED.  YOU MIGHT SEE THE 

645
00:27:36,936 --> 00:27:39,338
TINY DOT UP THERE IN THE PLAQUE 

646
00:27:39,338 --> 00:27:41,640
HOWEVER RIGHT ADJACENT TO IT IS 

647
00:27:41,640 --> 00:27:44,810
THE UPTAKE TO THE HEART AND IF 

648
00:27:44,810 --> 00:27:46,345
YOU USE GAL YUM 68 DO TO AT A 

649
00:27:46,345 --> 00:27:48,314
TIME YOU SEE THE ACTIVITY IN THE

650
00:27:48,314 --> 00:27:50,516
PLAQUE ITSELF. 

651
00:27:50,516 --> 00:27:52,218
YOU DON'T HAVE IT IN -- 

652
00:27:52,218 --> 00:27:55,955
EXTENSIVELY IN THE MYOCARDIUM.  

653
00:27:55,955 --> 00:27:58,124
IT COULD BE MUCH MORE SPECIFIC 

654
00:27:58,124 --> 00:28:01,060
SO AS I MENTIONED, THERE ARE 

655
00:28:01,060 --> 00:28:02,962
SOME BENEFITS TO NANOPARTICLES 

656
00:28:02,962 --> 00:28:04,697
AND IMAGING USING THEM IN 

657
00:28:04,697 --> 00:28:07,433
IMAGING THE ARTHROSCLEROSIS.  

658
00:28:07,433 --> 00:28:10,569
THEIR SMALL SIZE ALLOWS A HIGH 

659
00:28:10,569 --> 00:28:12,505
SURFACE AREA TO VOLUME.  IF 

660
00:28:12,505 --> 00:28:13,706
YOU'RE TRYING FUNCTIONALIZE IT, 

661
00:28:13,706 --> 00:28:16,208
IT CAN BE VERY USEFUL.  THERE 

662
00:28:16,208 --> 00:28:17,643
ARE MULTIPLE TARGETING 

663
00:28:17,643 --> 00:28:18,477
STRATEGIES. 

664
00:28:18,477 --> 00:28:21,647
YOU CAN HAVE PASSIVE TARGETING 

665
00:28:21,647 --> 00:28:24,483
BY THE MACROPHAGE PHAGOCYTOSIS, 

666
00:28:24,483 --> 00:28:25,951
YOU CAN HAVE THE AARON AGENTS, 

667
00:28:25,951 --> 00:28:31,290
YOU CAN ACTIVELY TARGET THE 

668
00:28:31,290 --> 00:28:32,057
LIGANDS WHICH IS WHAT WE'VE BEEN

669
00:28:32,057 --> 00:28:34,560
DOING AND AS I MENTIONED PUT 

670
00:28:34,560 --> 00:28:37,930
POTENTIALLY MULTIPLE LIGANDS PER

671
00:28:37,930 --> 00:28:41,667
PARTICLE AND POTENTIALLY, MAY 

672
00:28:41,667 --> 00:28:43,903
HAVE THEY ARE RAN ZEROSIC 

673
00:28:43,903 --> 00:28:45,037
CAPABILITIES.  I WILL SHOW YOU 

674
00:28:45,037 --> 00:28:47,873
WHERE A SINGLE AGENT IS USED TO 

675
00:28:47,873 --> 00:28:52,578
BOTH DIAGNOSE AND DELIVER A DRUG

676
00:28:52,578 --> 00:28:58,050
PAYLOA

677
00:28:58,050 --> 00:29:01,654
IN OUR LAB WITH THE DOCTOR WE'VE

678
00:29:01,654 --> 00:29:03,622
BEEN FOCUSING ON DENDRITES AND 

679
00:29:03,622 --> 00:29:08,694
COMBS.  USING A METAL BACKBONE 

680
00:29:08,694 --> 00:29:10,596
AND ARMS WE HAVE THIS COMB 

681
00:29:10,596 --> 00:29:13,666
STRUCTURE BUT HE IS ALSO LOOKED 

682
00:29:13,666 --> 00:29:16,535
AT GOLD CLUSTERS.  AND QUANTUM 

683
00:29:16,535 --> 00:29:18,737
AND C DOTS AND SOME OF THIS, THE

684
00:29:18,737 --> 00:29:21,640
GOLD CLUSTERS ARE NICE BECAUSE 

685
00:29:21,640 --> 00:29:23,676
YOU CAN COOK THEM UP IN YOUR OWN

686
00:29:23,676 --> 00:29:29,815
LAB WITH THE CNF COMB.  WE HAVE 

687
00:29:29,815 --> 00:29:32,852
A SYNTHESIS CHEMIST MAKING AND 

688
00:29:32,852 --> 00:29:36,388
THE SYNTHESIS CHEMIST IS WORLD 

689
00:29:36,388 --> 00:29:38,624
RENOWNED AND HAS INVENTED 

690
00:29:38,624 --> 00:29:40,392
SOMETHING CALLED O LOW PLEXUS.  

691
00:29:40,392 --> 00:29:41,660
I DON'T KNOW IF ANY OF YOU KNOW 

692
00:29:41,660 --> 00:29:42,828
WHAT THAT IS. 

693
00:29:42,828 --> 00:29:46,465
NO.  IF YOU ARE AN ACTOR OR AN 

694
00:29:46,465 --> 00:29:52,605
ACTRESS OR A WOMAN WHO GETS HER 

695
00:29:52,605 --> 00:30:00,012
HAIR DONE OR COLORED OR 

696
00:30:00,012 --> 00:30:00,779
PERMANPERMED 

697
00:30:00,779 --> 00:30:03,349
MANY TIMES.  SO REVLON BOUGHT 

698
00:30:03,349 --> 00:30:04,850
THAT AND IN THE MIDDLE OF OUR 

699
00:30:04,850 --> 00:30:07,553
RESEARCH PROJECT SO AS I SAID 

700
00:30:07,553 --> 00:30:08,954
I'M SURPRISE ME TAKES MY PHONE 

701
00:30:08,954 --> 00:30:11,590
CALLS WHEN I'M TELLING HIM I 

702
00:30:11,590 --> 00:30:13,259
NEED THAT COMB TYPE STUFF BUT 

703
00:30:13,259 --> 00:30:14,426
THAT'S A LITTLE SIDE BAR.  BUT 

704
00:30:14,426 --> 00:30:17,563
IN ANY CASE, YOU KNOW, GOLD 

705
00:30:17,563 --> 00:30:19,098
CLUSTERS ARE NICE BECAUSE YOU 

706
00:30:19,098 --> 00:30:21,667
CAN MAKE, WE'VE BEEN LOOKING AT 

707
00:30:21,667 --> 00:30:24,003
ALTERNATIVES IN CASE HE DECIDES 

708
00:30:24,003 --> 00:30:26,305
HE WANT TO GO LIVE ON A BEACH 

709
00:30:26,305 --> 00:30:28,607
SOMEWHERE WHERE WE COULD USE 

710
00:30:28,607 --> 00:30:31,543
GOLD CLUSTERS INSTEAD TO 

711
00:30:31,543 --> 00:30:34,546
FUNCTIONALIZE THEM WITH OUR 

712
00:30:34,546 --> 00:30:38,284
PEPTIDE.  BUT THIS IS THE AGENT,

713
00:30:38,284 --> 00:30:41,620
AND IT'S THIS IS THE, YOU KNOW, 

714
00:30:41,620 --> 00:30:44,290
IT FORMULATES INTO A COMB.  WE 

715
00:30:44,290 --> 00:30:47,226
FUNCTIONALIZE THIS WITH CANF AND

716
00:30:47,226 --> 00:30:52,364
THIS IS THE METHYL BACKBONE, 

717
00:30:52,364 --> 00:30:55,301
PALLY ETHYLENE ARMS AND WE USE 

718
00:30:55,301 --> 00:30:57,603
DOTA AND HERE'S COPPER 64. 

719
00:30:57,603 --> 00:31:02,608
THESE  GREEN DOTS ARE THE CANF. 

720
00:31:02,608 --> 00:31:04,710
AND THIS IS THE NAN PARTICLE AND

721
00:31:04,710 --> 00:31:08,213
IT BECOMES KIND OF LIKE A 

722
00:31:08,213 --> 00:31:10,683
MICELLE IN WATER.  ON THE 

723
00:31:10,683 --> 00:31:15,988
OUTSIDE.  AND THEN THE CNF ON 

724
00:31:15,988 --> 00:31:16,555
THE ARMS. 

725
00:31:16,555 --> 00:31:20,159
AND SO, YOU KNOW, AND THEN WE 

726
00:31:20,159 --> 00:31:22,428
PUT COPPER 64 ON THIS.  SO THIS 

727
00:31:22,428 --> 00:31:27,967
IS THE SIZE.  AND THEN ROUGHLY 

728
00:31:27,967 --> 00:31:33,205
ABOUT 35 CNF PEPTIDES PER 

729
00:31:33,205 --> 00:31:34,606
PARTICLE AND, YOU KNOW, ONE OF 

730
00:31:34,606 --> 00:31:37,509
THE QUESTIONS WAS HOW DID WE 

731
00:31:37,509 --> 00:31:40,612
DECIDE WHAT WE ENDED UP 

732
00:31:40,612 --> 00:31:44,249
DETERMINING WAS THAT 25% OF THE 

733
00:31:44,249 --> 00:31:47,386
ARMS WE HAVE FUNCTIONALIZED 25% 

734
00:31:47,386 --> 00:31:50,289
OF THE ARMS WITH CANF AND WE 

735
00:31:50,289 --> 00:31:51,156
TRIED MULTIPLE DIFFERENT 

736
00:31:51,156 --> 00:31:56,128
APPROACHES WE TRIED 5%, 10% AND,

737
00:31:56,128 --> 00:31:57,363
YOU KNOW, WE ACTUALLY WENT AT 

738
00:31:57,363 --> 00:32:01,066
ONE POINT UP TO 50% AND IT JUST 

739
00:32:01,066 --> 00:32:04,036
DIDN'T FIND IT AT ALL.  BUT 

740
00:32:04,036 --> 00:32:06,271
LOOKED AT BINDING CAPACITY AND 

741
00:32:06,271 --> 00:32:08,073
DID BLOCK AND SO IF YOU LOOK AT 

742
00:32:08,073 --> 00:32:14,747
THE 25% CNF ON THE COMB, AND THE

743
00:32:14,747 --> 00:32:16,548
BLOCKING MUCH MORE SIGNIFICANT 

744
00:32:16,548 --> 00:32:19,651
THAN 10% CNF COMB WITH BLOCKING.

745
00:32:19,651 --> 00:32:23,155
SO I ENDED UP WITH THIS 

746
00:32:23,155 --> 00:32:24,656
PARTICULAR AGENT IN -- THROUGH 

747
00:32:24,656 --> 00:32:26,992
THAT PROGRAM OF EXCELLENCE AND 

748
00:32:26,992 --> 00:32:28,293
THE AMOUNT OF NANO TECHNOLOGY 

749
00:32:28,293 --> 00:32:30,162
THAT WE BROUGHT INTO HUMANS.  

750
00:32:30,162 --> 00:32:33,632
AND SO WE THEN GOT BACK TO WHAT 

751
00:32:33,632 --> 00:32:36,568
ACTUALLY DOES THIS DO?  AND NPR 

752
00:32:36,568 --> 00:32:41,073
SEES THE RECEPTOR FOR THE CNP 

753
00:32:41,073 --> 00:32:42,908
FOR THE PEPTIDE AND SO THAT IS 

754
00:32:42,908 --> 00:32:49,448
WHAT TARGETS CNP TARGETS IN P 

755
00:32:49,448 --> 00:32:49,982
RSHR 

756
00:32:49,982 --> 00:32:53,419
C.  THIS IS ACTIVE.  SO WHAT WE 

757
00:32:53,419 --> 00:33:01,360
USE IS A 15 FRAGMENT.  AND THE 

758
00:33:01,360 --> 00:33:03,929
CANF IS A NONACTIVE FRAGMENT 

759
00:33:03,929 --> 00:33:05,564
WHICH IS THE PEPTIDE THAT WE PUT

760
00:33:05,564 --> 00:33:07,599
ON THESE PEG ARMS AND THAT IS 

761
00:33:07,599 --> 00:33:15,674
WHAT TARGETS NPRC.  AND US THE 

762
00:33:15,674 --> 00:33:17,443
OTHER THING I SHOULD MENTION IS 

763
00:33:17,443 --> 00:33:19,745
IT IS RESPONSIBLE FOR SMOOTH 

764
00:33:19,745 --> 00:33:20,679
MUSCLE CELL MIGRATION WHICH AS 

765
00:33:20,679 --> 00:33:22,614
WE DISCUSSED WITH OUR FINDINGS 

766
00:33:22,614 --> 00:33:26,218
WITH SOME OF OUR VASCULAR 

767
00:33:26,218 --> 00:33:27,686
BIOLOGISTS, SEEMS TO ACTUALLY 

768
00:33:27,686 --> 00:33:29,655
NOT ONLY CAUSE MIGRATION BUT 

769
00:33:29,655 --> 00:33:30,956
SOME PHENOTYPE CHANGE.  SO, YOU 

770
00:33:30,956 --> 00:33:33,759
KNOW, EARLY ON, WE STARTED 

771
00:33:33,759 --> 00:33:38,730
LOOKING AT SOME OF THE PA THTHOY

772
00:33:38,730 --> 00:33:41,200
OURSELVES.  WE PUBLISHED IN A 

773
00:33:41,200 --> 00:33:41,867
PATHOLOGY JOURNAL.  THERE WAS A 

774
00:33:41,867 --> 00:33:45,204
COUPLE OTHER GROUPS THAT HAD 

775
00:33:45,204 --> 00:33:49,708
NOTICED THAT NPRC IS PRESENT ON 

776
00:33:49,708 --> 00:33:52,344
MACROPHAGES AND ALSO IN PLAQUE 

777
00:33:52,344 --> 00:33:53,579
WITH VULNERABLE FEATURES.  BUT 

778
00:33:53,579 --> 00:33:55,280
SINCE WE NOTICED THIS AS WELL, 

779
00:33:55,280 --> 00:33:57,483
WE DECIDED TO PUBLISH IT AND YOU

780
00:33:57,483 --> 00:34:00,986
CAN SEE THAT THE RELATIVE NPRC 

781
00:34:00,986 --> 00:34:02,187
EXPRESSION WE LOOKED AT TISSUE 

782
00:34:02,187 --> 00:34:04,289
THAT WAS MINIMALLY DISEASED AND 

783
00:34:04,289 --> 00:34:08,694
MAXIMALLY DISEASED AND IT HAD A 

784
00:34:08,694 --> 00:34:09,661
GREATER PREVALENCE IN MAXIMAL 

785
00:34:09,661 --> 00:34:10,996
DISEASE AND ALSO MORE SO IN THE 

786
00:34:10,996 --> 00:34:15,400
DEEP INTIMA OR THE MEDIA IN 

787
00:34:15,400 --> 00:34:18,704
COMPARISON TO THE SUPERFICIAL 

788
00:34:18,704 --> 00:34:21,673
INTIMA AND MEDIA.  AND THIS WAS 

789
00:34:21,673 --> 00:34:28,147
WHERE WE STARTED TO TALK TO GARY

790
00:34:28,147 --> 00:34:32,284
OWENS WHO SUGGESTED THIS MAY BE 

791
00:34:32,284 --> 00:34:33,852
RESPONSIBLE NOT ONLY FOR 

792
00:34:33,852 --> 00:34:35,254
VASCULAR SMOOTH MUSCLE CELL 

793
00:34:35,254 --> 00:34:36,722
MIGRATION BUT EITHER A MARKER 

794
00:34:36,722 --> 00:34:40,259
THAT REMAINS ON THE CELLS AS IT 

795
00:34:40,259 --> 00:34:45,430
STARTS TO UNDERGO PHENOTYPE 

796
00:34:45,430 --> 00:34:49,368
CHANGE.  SO, HOW DID WE GET THIS

797
00:34:49,368 --> 00:34:52,938
INTO HUMANS?  WE TOOK A LOT OF 

798
00:34:52,938 --> 00:34:54,673
PRECLINICAL VALIDATION.  I 

799
00:34:54,673 --> 00:34:56,408
SHOWED YOU SOME OF THE BINDING 

800
00:34:56,408 --> 00:34:59,077
ASSAYS.  THE CELL STUDIES.  BUT 

801
00:34:59,077 --> 00:35:02,014
ALSO, YOU KNOW, WE DID ANIMAL 

802
00:35:02,014 --> 00:35:03,615
WORK.  WE INJURED RABBITS AND 

803
00:35:03,615 --> 00:35:07,019
GAVE THEM A WESTERN FED DIET AND

804
00:35:07,019 --> 00:35:08,153
DEMONSTRATED THAT THE RADIO 

805
00:35:08,153 --> 00:35:11,590
TRACER WAS TAKEN UP IN THESE 

806
00:35:11,590 --> 00:35:15,360
LESIONS.  DID SOME KNOCKOUT 

807
00:35:15,360 --> 00:35:17,462
MOUSE AND SOME ANGIOGENESIS 

808
00:35:17,462 --> 00:35:19,565
STUDIES AS WELL LOOK AT THE 

809
00:35:19,565 --> 00:35:21,500
PRESENCE, THE -- IT IS PRESENT 

810
00:35:21,500 --> 00:35:22,801
IN SOME ENDOTHELIAL CELLS WHO 

811
00:35:22,801 --> 00:35:26,838
WERE ABLE TO SEE THE DIFFERENCE 

812
00:35:26,838 --> 00:35:31,643
BETWEEN A HIGH ISCHEMIA MOUSE 

813
00:35:31,643 --> 00:35:34,112
AND ALSO LOOKED AT SOME GENE 

814
00:35:34,112 --> 00:35:37,182
EXPRESSION AND THEN BIO 

815
00:35:37,182 --> 00:35:39,585
DISTRIBUTION.  SO WHAT DO YOU 

816
00:35:39,585 --> 00:35:43,255
NEED TO GET AGENTS INTO THE FDA?

817
00:35:43,255 --> 00:35:48,060
WELL YOU NEED A GMP FACILITY FOR

818
00:35:48,060 --> 00:35:48,694
RADIO LABELING BECAUSE YOU'RE 

819
00:35:48,694 --> 00:35:52,864
GOING TO BE BRINGING THIS INTO 

820
00:35:52,864 --> 00:35:53,665
HUMANS. 

821
00:35:53,665 --> 00:35:56,268
YOU ALSO NEED TO ASSESS 

822
00:35:56,268 --> 00:36:00,339
SYMMETRY.  TOXICITY ASSESSMENT. 

823
00:36:00,339 --> 00:36:01,707
IT HELPS IF YOU HAVE A LAB AND I

824
00:36:01,707 --> 00:36:03,242
WILL TELL YOU ABOUT THAT IN A 

825
00:36:03,242 --> 00:36:04,643
MINUTE BUT YOU DON'T HAVE TO 

826
00:36:04,643 --> 00:36:08,113
HAVE A GOP LAB FOR TOX, FOR 

827
00:36:08,113 --> 00:36:10,616
ANIMALS.  IF IT'S LESS THAN 100 

828
00:36:10,616 --> 00:36:12,251
MICROGRAMS IF WHAT YOU PLAN TO 

829
00:36:12,251 --> 00:36:14,753
INJECT INTO A HUMAN IS LESS THAN

830
00:36:14,753 --> 00:36:17,055
100 MICRO PROGRAMS YOU CAN APPLY

831
00:36:17,055 --> 00:36:19,424
FOR AN EIND AND THAT CAN HELP 

832
00:36:19,424 --> 00:36:21,293
YOU OUT A BIT THEN YOU DON'T 

833
00:36:21,293 --> 00:36:23,595
NEED A LARGE ANIMAL MODEL YOU 

834
00:36:23,595 --> 00:36:25,497
CAN GO WITH A SINGLE MODEL.  I 

835
00:36:25,497 --> 00:36:28,567
WILL TELL YOU THE STORY, YOU 

836
00:36:28,567 --> 00:36:32,704
WILL HAVE A PRE-IND MEETING WITH

837
00:36:32,704 --> 00:36:35,274
THE FDA BUT AT THE TIME WE WERE 

838
00:36:35,274 --> 00:36:36,742
WORKING WITH MIKE WELCH AND -- 

839
00:36:36,742 --> 00:36:38,777
HOW MANY OF YOU KNEW MIKE WELCH?

840
00:36:38,777 --> 00:36:40,512
YEAH, I'M SURE YOU DO AND MIKE 

841
00:36:40,512 --> 00:36:42,881
WAS ALWAYS VERY OPINIONATED.  

842
00:36:42,881 --> 00:36:43,982
AND SO IT WAS THE WEDNESDAY 

843
00:36:43,982 --> 00:36:47,719
BEFORE HE DIED.  AND HE CALLS US

844
00:36:47,719 --> 00:36:50,555
ALL INTO THE STEP DOWN UNIT 

845
00:36:50,555 --> 00:36:55,327
WHERE HE IS.  HE HAS AN 

846
00:36:55,327 --> 00:36:57,095
OBJECTION FRACTION OF 20% AND 

847
00:36:57,095 --> 00:36:59,731
BLADDER CANCER AND A 

848
00:36:59,731 --> 00:37:00,866
CARDIODEFIBRILLATOR AND I THINK 

849
00:37:00,866 --> 00:37:03,669
HE BELIEVES THE END IS NEAR AND 

850
00:37:03,669 --> 00:37:05,671
HE CALLS US INTO THIS ROOM. 

851
00:37:05,671 --> 00:37:08,307
AND HE NEVER TOLD US HOW MUCH 

852
00:37:08,307 --> 00:37:09,308
MONEY WE HAD EVEN THOUGH WE WERE

853
00:37:09,308 --> 00:37:11,376
PROGRAM PROJECT DIRECTORS.  

854
00:37:11,376 --> 00:37:12,978
HE -- HE WAS FINALLY TELLING US,

855
00:37:12,978 --> 00:37:16,048
THIS IS WHAT YOU HAVE, THIS IS 

856
00:37:16,048 --> 00:37:17,015
WHAT YOU SHOULD DO AND ROB SAYS 

857
00:37:17,015 --> 00:37:20,919
WE WERE TALKING ABOUT THIS AND 

858
00:37:20,919 --> 00:37:23,021
I'M LIKE, ROB, ASK HIM, SHOULD 

859
00:37:23,021 --> 00:37:25,424
WE GET A PRE-IND MEETING AND 

860
00:37:25,424 --> 00:37:29,094
MIKE GOES, IN HIS BRITISH 

861
00:37:29,094 --> 00:37:34,700
ACCENT, NO, NO PRE-IND.  NO.  SO

862
00:37:34,700 --> 00:37:37,102
OVER THE WEEKEND HE PASSED AWAY 

863
00:37:37,102 --> 00:37:38,970
AND THEN TWO YEARS LATER WE'RE 

864
00:37:38,970 --> 00:37:40,605
TALKING TO OUR PROJECT OFFICER, 

865
00:37:40,605 --> 00:37:41,940
PROGRAM OFFICER DENNIS BUXTON AT

866
00:37:41,940 --> 00:37:45,077
THE NHLBI AND WE'RE ABOUT TO 

867
00:37:45,077 --> 00:37:48,113
SUBMIT THIS TO THE FDA AND HE 

868
00:37:48,113 --> 00:37:50,482
SAYS I THINK YOU NEED A PRE-IND 

869
00:37:50,482 --> 00:37:51,783
MEETING AND ROB AND I JUST LOOK 

870
00:37:51,783 --> 00:37:53,819
AT EACH OTHER AND HE GOES WHAT? 

871
00:37:53,819 --> 00:37:55,921
WHAT'S WRONG?  AND ROB GOES, 

872
00:37:55,921 --> 00:37:57,656
WELL MIKE TOLD US NOT TO GET 

873
00:37:57,656 --> 00:38:01,560
ONE.  AND THERE'S SILENCE AND 

874
00:38:01,560 --> 00:38:07,766
THEN HE SAYS, HE GOES WHEN DID 

875
00:38:07,766 --> 00:38:09,568
YOU TALK TO MIKE?  LIKE WE WERE 

876
00:38:09,568 --> 00:38:11,069
HOLDING THESE SEANCES AND TRYING

877
00:38:11,069 --> 00:38:13,071
TO GET INFORMATION FROM MIKE AND

878
00:38:13,071 --> 00:38:14,706
I THINK IT WAS JUST BECAUSE IT 

879
00:38:14,706 --> 00:38:16,942
WAS ON HIS DEATHBED THAT WE FELT

880
00:38:16,942 --> 00:38:18,910
THIS WAS ONE OF HIS LAST DYING 

881
00:38:18,910 --> 00:38:19,978
WORDS THAT WE HAVE TO DO IT AND 

882
00:38:19,978 --> 00:38:23,181
WE JUST SUBMITTED IT AND WE WERE

883
00:38:23,181 --> 00:38:27,586
VERY FORTUNATE WE HAD NOT GONE 

884
00:38:27,586 --> 00:38:29,654
TO SEVENTH WAVE WE DID IT ALL 

885
00:38:29,654 --> 00:38:31,456
IN-HOUSE.  THEY DID AN EXCELLENT

886
00:38:31,456 --> 00:38:33,258
JOB THE PAPERWORK WAS VERY 

887
00:38:33,258 --> 00:38:34,726
THOROUGH THEY DID SEND SOME 

888
00:38:34,726 --> 00:38:39,498
THINGS OUT TO CHARLES RIVER FOR 

889
00:38:39,498 --> 00:38:42,367
BLOOD, QUESTIONS ON BLOOD TOX.  

890
00:38:42,367 --> 00:38:43,201
BUT IT WENT THROUGH.  THERE WERE

891
00:38:43,201 --> 00:38:46,238
A LOT OF QUESTIONS.  BUT REALLY 

892
00:38:46,238 --> 00:38:47,172
WENT THROUGH, YOU KNOW, MUCH 

893
00:38:47,172 --> 00:38:52,611
MORE EASILY THAN I THOUGHT WOULD

894
00:38:52,611 --> 00:38:55,714
BE.  EVEN THOUGH WE DIDN'T USE 

895
00:38:55,714 --> 00:38:59,084
THE GLP.  I JUST WANT TO TALK 

896
00:38:59,084 --> 00:39:02,120
ABOUT THE DOSE SYMMETRY AND THE 

897
00:39:02,120 --> 00:39:04,489
BUY YOU DISTRIBUTION. 

898
00:39:04,489 --> 00:39:07,325
THIS IS IN MICE AND WHEN WE 

899
00:39:07,325 --> 00:39:09,127
FIRST DID THIS IN MICE THE 

900
00:39:09,127 --> 00:39:14,199
CRITICAL ORGAN WAS BONE SURFACE 

901
00:39:14,199 --> 00:39:15,100
THESE ARE YOUNG MICE AND YOU SEE

902
00:39:15,100 --> 00:39:17,903
THE UPTAKE IN THE END PLATES OF 

903
00:39:17,903 --> 00:39:21,673
BONE.  NPRC IS ALSO RESPONSIBLE 

904
00:39:21,673 --> 00:39:23,842
FOR DEPOSITING BONE WHICH MAKES 

905
00:39:23,842 --> 00:39:24,810
YOU WONDER IF THERE ARE OTHER 

906
00:39:24,810 --> 00:39:27,946
ROLES THAT IT PLAYS IN THE 

907
00:39:27,946 --> 00:39:28,647
ARTHROSCLEROSIS WHEN YOU DO 

908
00:39:28,647 --> 00:39:31,716
THESE CAROTID IMAGING IN PATIENT

909
00:39:31,716 --> 00:39:33,185
WHO IS HAVE DEGENERATIVE CHANGE 

910
00:39:33,185 --> 00:39:37,456
IN THE SPAIN YOU  -- SPINE YOU 

911
00:39:37,456 --> 00:39:38,757
SEE IT IN THE SPINE ITSELF. 

912
00:39:38,757 --> 00:39:40,759
IT'S AT THE END PLAITS AND SO --

913
00:39:40,759 --> 00:39:45,997
BUT I HAVE TO SAY IN -- TOX 

914
00:39:45,997 --> 00:39:49,067
ACTUALLY IN THE OTHER ANIMALS 

915
00:39:49,067 --> 00:39:52,704
WAS FINE.  I DON'T KNOW IF I 

916
00:39:52,704 --> 00:39:54,039
HAVE THE SLIDE BUT IF HUMANS YOU

917
00:39:54,039 --> 00:39:55,941
DON'T HAVE -- BONE IS NOT A 

918
00:39:55,941 --> 00:39:57,275
TARGET ORGAN AND I THINK THIS IS

919
00:39:57,275 --> 00:39:58,743
BECAUSE WE WERE LOOKING AT 

920
00:39:58,743 --> 00:39:59,978
ADULTS, IN OTHER WORDS, WE 

921
00:39:59,978 --> 00:40:03,114
WEREN'T LOOKING AT PEOPLE WHO 

922
00:40:03,114 --> 00:40:04,349
WERE LAYING DOWN NEW BONE AS 

923
00:40:04,349 --> 00:40:06,518
THEY START TO GROW.  THE 

924
00:40:06,518 --> 00:40:08,353
KNOCKOUT MICE ACTUALLY HAVE 

925
00:40:08,353 --> 00:40:09,488
SKELETAL DEFORMITIES WHICH IS 

926
00:40:09,488 --> 00:40:10,455
VERY INTERESTING.  SO ONE THING 

927
00:40:10,455 --> 00:40:12,958
YOU DO HAVE TO EXPECT, WHEN YOU 

928
00:40:12,958 --> 00:40:16,094
ARE SUBMITTING TO THE FDA IS 

929
00:40:16,094 --> 00:40:17,662
THAT YOU WILL BE WRITING A LOT 

930
00:40:17,662 --> 00:40:23,201
OF SOPS.  YOU KNOW, UCSB HAD NOT

931
00:40:23,201 --> 00:40:27,038
BEEN A GMP FACILITY BEFORE.  

932
00:40:27,038 --> 00:40:29,774
UCSB IS WHERE YOUR PHYSICIST 

933
00:40:29,774 --> 00:40:31,843
CHEMIST IS SO WE FLEW OUT AND 

934
00:40:31,843 --> 00:40:37,315
THERE'S AND HE -- AND HELPED TH 

935
00:40:37,315 --> 00:40:38,917
WITH THE FACILITY. 

936
00:40:38,917 --> 00:40:40,919
WE DID EVERYTHING BACK AT WASH U

937
00:40:40,919 --> 00:40:46,258
BUT ESSENTIAL LYCETT UP ABOUT 70

938
00:40:46,258 --> 00:40:48,293
SOPS FOR THEM AND CLOSE TO ONE 

939
00:40:48,293 --> 00:40:51,696
HUNDRED FOR US FOR THE GMP 

940
00:40:51,696 --> 00:40:54,332
LABELING AND THEN HAD THE EIND 

941
00:40:54,332 --> 00:40:57,669
SUBMISSION WHICH ALSO INCLUDES 

942
00:40:57,669 --> 00:41:02,941
AN IRB SUBMISSION AND THEN SET 

943
00:41:02,941 --> 00:41:05,777
UP THE RELEASE QC.  ALL OF THIS 

944
00:41:05,777 --> 00:41:07,812
IS NOW FAIRLY ROUTINE THAT WE'VE

945
00:41:07,812 --> 00:41:10,849
DONE IT.  YOU KNOW, 60 OR 70 

946
00:41:10,849 --> 00:41:13,084
TIMES BUT THE FIRST TIME THAT WE

947
00:41:13,084 --> 00:41:18,356
DID THIS, YOU KNOW, IT'S -- IT 

948
00:41:18,356 --> 00:41:21,226
WAS QUITE LABORIOUS AND THIS WAS

949
00:41:21,226 --> 00:41:25,430
THE EIND FDA SUBMISSION FOR THE 

950
00:41:25,430 --> 00:41:27,432
AGENT AND THESE FIRST THREE, THE

951
00:41:27,432 --> 00:41:28,600
SUBMISSION, EVERYTHING USED TO 

952
00:41:28,600 --> 00:41:29,834
BE DONE IN PAPER.  NOW YOU CAN 

953
00:41:29,834 --> 00:41:31,736
ACTUALLY UPLOAD.  THERE'S A 

954
00:41:31,736 --> 00:41:33,371
WEBSITE WHICH MAKES IT A LOT 

955
00:41:33,371 --> 00:41:34,906
EASIER.  AND THEY HAD TO BE 

956
00:41:34,906 --> 00:41:36,174
COLOR-CODED, YOU KNOW, THE 

957
00:41:36,174 --> 00:41:38,209
BINDERS HAD TO BE LIKE IN RED, 

958
00:41:38,209 --> 00:41:39,811
ORANGE AND GREEN.  AND THIS WAS 

959
00:41:39,811 --> 00:41:41,279
THE SUBMISSION.  AND THESE ARE 

960
00:41:41,279 --> 00:41:43,848
THE ANSWERS TO THE QUERIES.  SO 

961
00:41:43,848 --> 00:41:46,084
WE ANSWERED THE QUERIES.  BUT IN

962
00:41:46,084 --> 00:41:47,185
BETWEEN HERE AND HERE WAS VERY 

963
00:41:47,185 --> 00:41:49,020
INTERESTING.  YOU KNOW, THE FDA 

964
00:41:49,020 --> 00:41:51,189
HAS 30 DAYS AND THEY USUALLY, 

965
00:41:51,189 --> 00:41:53,191
AFTER THE 30TH DAY IF YOU DON'T 

966
00:41:53,191 --> 00:41:56,962
HEAR BACK FROM THEM, YOU'RE HOME

967
00:41:56,962 --> 00:41:59,564
FREE BUT WHAT USUALLY HAPPENS IS

968
00:41:59,564 --> 00:42:02,734
ON DAY 29 YOU GET AN E-MAIL THAT

969
00:42:02,734 --> 00:42:04,369
HAS 17 QUERIES AND THENTAIL 

970
00:42:04,369 --> 00:42:08,406
THEY'LL SAY CAN YOU MEET WITH US

971
00:42:08,406 --> 00:42:09,774
TOMORROW AFTERNOON AT 2 O'CLOCK 

972
00:42:09,774 --> 00:42:11,176
ON FRIDAY. 

973
00:42:11,176 --> 00:42:13,311
AND ANSWER ALL OF THESE 

974
00:42:13,311 --> 00:42:14,546
QUESTIONS AND SO FOR THE LAST 

975
00:42:14,546 --> 00:42:15,680
HALF OF THE DAY YOU'RE 

976
00:42:15,680 --> 00:42:17,515
SCRAMBLING AROUND TRYING TO FIND

977
00:42:17,515 --> 00:42:21,920
OUT WHY, YOU KNOW, THIS FPLC'S 

978
00:42:21,920 --> 00:42:24,122
PEAK WAS THIS WAY AND WHATNOT 

979
00:42:24,122 --> 00:42:27,359
AND SO, YOU KNOW, THERE ARE MANY

980
00:42:27,359 --> 00:42:30,528
INDIVIDUALS WHO ARE VERY HELPFUL

981
00:42:30,528 --> 00:42:32,664
WHO, I DON'T KNOW HOW MANY OF 

982
00:42:32,664 --> 00:42:35,934
YOU KNOW SALLY SCHWARZ WE KNOW 

983
00:42:35,934 --> 00:42:37,836
HER BECAUSE SHE WAS PRESIDENT OF

984
00:42:37,836 --> 00:42:41,172
THE SNMMI BUT SHE'S A RADIO 

985
00:42:41,172 --> 00:42:42,340
PHARMACIST.  BUT SHE WAS 

986
00:42:42,340 --> 00:42:43,708
INVALUABLE I HAVE HER SITTING 

987
00:42:43,708 --> 00:42:44,075
NEXT TO ME. 

988
00:42:44,075 --> 00:42:45,644
AND THIS IS THE DAYS BEFORE ZOOM

989
00:42:45,644 --> 00:42:49,381
WE'D HAVE A POLY CON AND THE FDA

990
00:42:49,381 --> 00:42:50,749
WOULD BE ASKING ME QUESTIONS AND

991
00:42:50,749 --> 00:42:55,387
ILL -- I WOULD START TO SAY 

992
00:42:55,387 --> 00:42:57,622
SOMETHING AND SHE WOULD SAY SAY 

993
00:42:57,622 --> 00:43:01,259
THIS, SAY THIS.  IT REALLY DOES 

994
00:43:01,259 --> 00:43:03,395
TAKE A TEAM TO GO THROUGH TO GET

995
00:43:03,395 --> 00:43:07,332
THINGS INTO, THROUGH THE FDA AND

996
00:43:07,332 --> 00:43:10,669
TO HUMANS.  AND SO AFTER THAT 

997
00:43:10,669 --> 00:43:14,639
FIRST EIND WE WERE ABLE TO DO 

998
00:43:14,639 --> 00:43:15,640
NORMAL VOLUNTEERS FOR HUMAN 

999
00:43:15,640 --> 00:43:16,841
DISTRIBUTION AND DOSE SYMMETRY 

1000
00:43:16,841 --> 00:43:19,678
AND WE DID EIGHT OF THESE AND 

1001
00:43:19,678 --> 00:43:22,013
EMBARKED ON A SORT OF A PROOF OF

1002
00:43:22,013 --> 00:43:26,017
CONCEPT STUDY WITH 44 PATIENTS. 

1003
00:43:26,017 --> 00:43:27,852
I THINK WE HAD PLANNED FOR 50 

1004
00:43:27,852 --> 00:43:33,058
BUT WE GOT TO 44 BEFORE OUR RO 1

1005
00:43:33,058 --> 00:43:34,659
FUNDING RAN OUT FOR OUR PROJECT 

1006
00:43:34,659 --> 00:43:37,829
AND THESE ARE PATIENTS WHO ARE 

1007
00:43:37,829 --> 00:43:39,698
SCHEDULED FOR ENDOOR DIRECT MY 

1008
00:43:39,698 --> 00:43:41,700
AND SOME OF THEM WOULD GO AND 

1009
00:43:41,700 --> 00:43:43,601
SOME OF THEM WOULDN'T AND WE 

1010
00:43:43,601 --> 00:43:46,304
WOULD -- THE. 

1011
00:43:46,304 --> 00:43:52,477
ONES THAT WENT ONTO SURGERY WE 

1012
00:43:52,477 --> 00:43:53,645
WOULD TAKE THE PLAQUE AND DO 

1013
00:43:53,645 --> 00:43:57,082
CELL COUNTS AND IT HAD A VERY 

1014
00:43:57,082 --> 00:43:58,983
NICE CORRELATION TO THE UPTAKE 

1015
00:43:58,983 --> 00:44:00,351
IN THESE -- IN THE PLAQUE AND I 

1016
00:44:00,351 --> 00:44:01,920
WILL SHOW YOU THAT BUT THEY ALSO

1017
00:44:01,920 --> 00:44:04,022
GOT AN MRI SO YOU COULD SEE THE 

1018
00:44:04,022 --> 00:44:07,592
PLAQUE COMPOSITION BY MRI AND 

1019
00:44:07,592 --> 00:44:08,226
THEN WHETHER OR NOT, WHAT THE 

1020
00:44:08,226 --> 00:44:10,995
UPTAKE WAS USING THE RADIO 

1021
00:44:10,995 --> 00:44:11,663
TRACER.  

1022
00:44:11,663 --> 00:44:12,997
SO THIS IS WHERE I WAS GOING TO 

1023
00:44:12,997 --> 00:44:14,432
SHOW YOU, IT'S KIND OF 

1024
00:44:14,432 --> 00:44:15,734
INTERESTING THAT THE CRITICAL 

1025
00:44:15,734 --> 00:44:21,639
ORGAN WAS THE LIVER WHICH IS NOT

1026
00:44:21,639 --> 00:44:23,808
SURPRISING BECAUSE OF ALL THAT 

1027
00:44:23,808 --> 00:44:25,643
PEG BUT THE BONE DIDN'T SHOW 

1028
00:44:25,643 --> 00:44:28,012
MUCH UPTAKE AND I THINK PART OF 

1029
00:44:28,012 --> 00:44:32,684
THIS IS BECAUSE YOU HAVE HUMANS 

1030
00:44:32,684 --> 00:44:34,586
WHO ARE FULLY DEVELOPED 

1031
00:44:34,586 --> 00:44:36,020
SKELETALLY AND THE CRITICAL 

1032
00:44:36,020 --> 00:44:38,823
ORGAN WAS THE LIVER.  SO, AS I 

1033
00:44:38,823 --> 00:44:42,227
MENTIONED, WE DID THIS STUDY TO,

1034
00:44:42,227 --> 00:44:43,862
SO WE NOW HAVE -- WE ARE ON OUR 

1035
00:44:43,862 --> 00:44:45,630
SECOND STUDY.  THE FIRST ONE WAS

1036
00:44:45,630 --> 00:44:48,133
JUST SORT OF A FEASIBILITY STUDY

1037
00:44:48,133 --> 00:44:49,367
BUT THE SECOND IS LOOKING AT 

1038
00:44:49,367 --> 00:44:51,736
PATIENT OUTCOMES.  AND THIS IS 

1039
00:44:51,736 --> 00:44:53,171
WHAT WE'RE DOING WITH SEEDERS 

1040
00:44:53,171 --> 00:44:55,707
WITH THE TWO OBJECTIVES ONE IS 

1041
00:44:55,707 --> 00:44:57,442
TO DEMONSTRATE AND WE CAN SHIP 

1042
00:44:57,442 --> 00:45:00,378
OUT TO CALIFORNIA AND HAVE A 

1043
00:45:00,378 --> 00:45:02,447
SIMILAR PET MR EXAM THERE, 

1044
00:45:02,447 --> 00:45:04,649
FEASIBILITY IN THAT WAY, BUT 

1045
00:45:04,649 --> 00:45:07,085
THEN ALSO TO TAKE PATIENTS WHO 

1046
00:45:07,085 --> 00:45:10,655
HAVE A STENOSIS OF 70% DIAMETER 

1047
00:45:10,655 --> 00:45:12,657
AND TAKE PATIENTS WHO ARE EITHER

1048
00:45:12,657 --> 00:45:15,593
BEING TREATED MEDICALLY OR 

1049
00:45:15,593 --> 00:45:17,262
SURGICALLY AND WITH THE SURGICAL

1050
00:45:17,262 --> 00:45:18,096
PATIENTS WE'RE LOOK AT THE 

1051
00:45:18,096 --> 00:45:24,269
PLAQUE BUT WITH THE MEDICAL 

1052
00:45:24,269 --> 00:45:26,805
PATIENTS WE IMAGE THEM BEFORE 

1053
00:45:26,805 --> 00:45:28,640
OPTIMAL MEDICAL THERAPY AND THEN

1054
00:45:28,640 --> 00:45:31,242
18 MONTHS LATER AND CALL THEM 

1055
00:45:31,242 --> 00:45:32,210
ALONG THE WAY, EVERY THREE 

1056
00:45:32,210 --> 00:45:35,380
MONTHS TO MAKE SURE THAT THEY 

1057
00:45:35,380 --> 00:45:37,649
ARE TAKING THEIR OPTIMAL MEDICAL

1058
00:45:37,649 --> 00:45:40,652
THERAPY, THEIR STATIN AND THEIR 

1059
00:45:40,652 --> 00:45:43,288
OTHER, YOU KNOW, 

1060
00:45:43,288 --> 00:45:45,323
ANTIHYPERTENSIVES AND THEIR 

1061
00:45:45,323 --> 00:45:46,558
ANTIDIABETIC DRUGS TO MAKE SURE 

1062
00:45:46,558 --> 00:45:50,161
THAT AND THEN LOOK AT THE 

1063
00:45:50,161 --> 00:45:51,029
DIFFERENCE.  SO THE RESULTS, ONE

1064
00:45:51,029 --> 00:45:54,132
OF THE RESULTS OF OUR FIRST 

1065
00:45:54,132 --> 00:45:57,669
STUDIES WAS THAT OF THE 

1066
00:45:57,669 --> 00:46:00,805
PATIENCES  PATIENTS WHO WERE 

1067
00:46:00,805 --> 00:46:01,072
ENROLLED. 

1068
00:46:01,072 --> 00:46:07,579
WE HAD 19, I THINK 15 PATIENTS 

1069
00:46:07,579 --> 00:46:08,947
WHO WENT ONTO SURGERY AND OF 

1070
00:46:08,947 --> 00:46:11,316
THESE 15 PATIENTS THAT 

1071
00:46:11,316 --> 00:46:11,916
UNDERSTOOD WENT THE PLAQUE 

1072
00:46:11,916 --> 00:46:12,750
COLLECTION WITH THE STAINING AND

1073
00:46:12,750 --> 00:46:15,486
CELL COUNTING SHOWED A NICE 

1074
00:46:15,486 --> 00:46:17,388
CORRELATION BETWEEN THE SUV AND 

1075
00:46:17,388 --> 00:46:20,658
THE PRESENCE OF THE MPRC.  AND 

1076
00:46:20,658 --> 00:46:22,794
THEN RETROSPECTIVELY WE WENT 

1077
00:46:22,794 --> 00:46:25,530
BACK AND WENT DOES THIS MAKE ANY

1078
00:46:25,530 --> 00:46:27,932
DIFFERENCES IS SUV ELEVATION 

1079
00:46:27,932 --> 00:46:29,634
CORRELATE WITH ANYTHING AND THIS

1080
00:46:29,634 --> 00:46:32,837
WAS REALLY MORE OF A TREND.  BUT

1081
00:46:32,837 --> 00:46:35,506
THE FIVE PATIENTS THAT HAD 

1082
00:46:35,506 --> 00:46:41,546
EVENTS DID HAVE AN SUV THAT WAS 

1083
00:46:41,546 --> 00:46:43,047
HIGHER THAN THE 22 WHO DID NOT 

1084
00:46:43,047 --> 00:46:45,049
HAVE AN EVENT SO THAT PROMPTED 

1085
00:46:45,049 --> 00:46:47,418
US TO EMBARK ON OUR SECOND STUDY

1086
00:46:47,418 --> 00:46:49,320
LOOKING AT OUTCOMES.  WHAT DO 

1087
00:46:49,320 --> 00:46:50,955
THESE IMAGES LOOK LIKE?  YOU CAN

1088
00:46:50,955 --> 00:46:55,193
SEE UPTAKE IN ARTHROSCLEROSIS, 

1089
00:46:55,193 --> 00:46:58,696
THIS IS A PATIENT, 86-YEAR-OLD 

1090
00:46:58,696 --> 00:47:03,368
WHO WENT TO SURGERY AND THE 

1091
00:47:03,368 --> 00:47:05,937
IMAGES BELOW BETWEEN THE 

1092
00:47:05,937 --> 00:47:09,240
MAXIMALLY DISEASED CAROTID AND 

1093
00:47:09,240 --> 00:47:11,242
THE MINIMALLY DISEASED YOU CAN 

1094
00:47:11,242 --> 00:47:13,444
NICELY SEE WE HAVE CD 68 WHICH 

1095
00:47:13,444 --> 00:47:16,681
IS A MARKER FOR MACROPHAGES AND 

1096
00:47:16,681 --> 00:47:19,117
NPRC WHICH IS THE, YOU KNOW, WE 

1097
00:47:19,117 --> 00:47:22,687
HAVE A MARKER FOR NPRC.  AND 

1098
00:47:22,687 --> 00:47:26,524
WHEN YOU COLOCALIZE, YOU KNOW, 

1099
00:47:26,524 --> 00:47:28,526
LOOKS LIKE THEY'RE PRINCIPALLY 

1100
00:47:28,526 --> 00:47:30,428
IN MACROPHAGES BUT YOU CAN -- WE

1101
00:47:30,428 --> 00:47:33,564
ALSO -- THERE'S -- THIS IS A 

1102
00:47:33,564 --> 00:47:37,468
HIGH RESOLUTION OF NPRC WITH CD 

1103
00:47:37,468 --> 00:47:39,971
68 AND YOU CAN ALSO SEE IN THE 

1104
00:47:39,971 --> 00:47:42,440
PLAQUE, REALLY NOT MUCH THERE, 

1105
00:47:42,440 --> 00:47:46,678
NOT MUCH NPRC, NOT MUCH CD 68 

1106
00:47:46,678 --> 00:47:47,712
AND SO THE DIFFERENCE BETWEEN 

1107
00:47:47,712 --> 00:47:50,682
THE DISEASE AND THE NONDISEASED 

1108
00:47:50,682 --> 00:47:54,786
PORTIONS OF THIS WOMAN'S CAROTID

1109
00:47:54,786 --> 00:47:57,188
ARTERY.  AND JUST, AND SOME 

1110
00:47:57,188 --> 00:47:59,490
OTHER EXAMPLES, THIS IS A 

1111
00:47:59,490 --> 00:48:00,758
REFUSED PET MR IMAGE WHERE YOU 

1112
00:48:00,758 --> 00:48:04,395
CAN SEE THE UPTAKE IN THE 

1113
00:48:04,395 --> 00:48:05,663
ARTHROSCLEROSIS AND IN A 

1114
00:48:05,663 --> 00:48:06,497
SEPARATE PATIENT BUT SIMILAR 

1115
00:48:06,497 --> 00:48:07,865
WHERE YOU CAN SEE THE 

1116
00:48:07,865 --> 00:48:09,667
COLOCALIZATION OF THE 

1117
00:48:09,667 --> 00:48:16,674
MACROPHAGES IN NPRC AND THEN WE 

1118
00:48:16,674 --> 00:48:19,711
THE AUTORAID YOL RAH FEW AND YOU

1119
00:48:19,711 --> 00:48:21,279
CAN SEE IT'S BEING BLOCKED. 

1120
00:48:21,279 --> 00:48:22,513
I'M GOING TO TALK TO YOU 

1121
00:48:22,513 --> 00:48:24,349
BRIEFLY.  WE'RE GETTING CLOSE TO

1122
00:48:24,349 --> 00:48:27,752
THE END OF THE TALK.  

1123
00:48:27,752 --> 00:48:28,820
ABOUT MYOCARDIAL INFLAMMATION 

1124
00:48:28,820 --> 00:48:33,391
AND CCR 2 AND CCR 2 IS 

1125
00:48:33,391 --> 00:48:36,361
MONOCYTES: AND SO, IT PLAYS A 

1126
00:48:36,361 --> 00:48:38,396
CRITICAL ROLE IN DEFENSIVE 

1127
00:48:38,396 --> 00:48:39,630
MULTIPLE DISEASES AND WE'VE BEEN

1128
00:48:39,630 --> 00:48:42,200
USING IT TO LOOK AT 

1129
00:48:42,200 --> 00:48:44,035
ARTHROSCLEROSIS BUT ALSO LOOKING

1130
00:48:44,035 --> 00:48:48,873
AT PATIENTS POST MYOCARDIAL 

1131
00:48:48,873 --> 00:48:52,577
INFARCTION.  AND THE TOP PATIENT

1132
00:48:52,577 --> 00:48:54,379
HERE IS A NORMAL CONTROL BOTH A 

1133
00:48:54,379 --> 00:48:58,683
SPEC STUDY AND THEN THE CCR 2 

1134
00:48:58,683 --> 00:49:02,286
PET STUDY AND YOU CAN SEE NO CCR

1135
00:49:02,286 --> 00:49:05,490
2 UPTAKE BECAUSE PRESUMABLY NO 

1136
00:49:05,490 --> 00:49:08,159
INFLAMMATION AND THE SPEC SHOWS 

1137
00:49:08,159 --> 00:49:13,664
MY OWE CARDIAL ACTIVITY IN THE 

1138
00:49:13,664 --> 00:49:14,665
NORMAL MYOCARDIUM. 

1139
00:49:14,665 --> 00:49:18,369
AND THIS IS DAY 101 AND YOU CAN 

1140
00:49:18,369 --> 00:49:21,005
SEE THIS IS THE AREA OF 

1141
00:49:21,005 --> 00:49:22,040
MYOCARDIAL INFARCTION AND THIS 

1142
00:49:22,040 --> 00:49:25,243
IS TAKEN UP IN THE AREA OF 

1143
00:49:25,243 --> 00:49:26,411
MYOCARDIAL INFARCTION AND SO, 

1144
00:49:26,411 --> 00:49:29,614
OUR HOPE IS THAT IT COULD TELL 

1145
00:49:29,614 --> 00:49:32,250
US SOMETHING ABOUT MYOCARDIAL 

1146
00:49:32,250 --> 00:49:33,651
INFARCTION EVOLUTION AND THIS 

1147
00:49:33,651 --> 00:49:36,754
WAS PUBLISHED BY KORIE LEVINE 

1148
00:49:36,754 --> 00:49:37,955
AND ROB IN NATURE CARDIOVASCULAR

1149
00:49:37,955 --> 00:49:39,824
RESEARCH JUST THIS PAST YEAR.  

1150
00:49:39,824 --> 00:49:42,894
AND, YOU KNOW, YOU CAN LOOK AT 

1151
00:49:42,894 --> 00:49:45,229
THE SUV DIFFERENCES BETWEEN THE 

1152
00:49:45,229 --> 00:49:47,065
INFARCT AND THE REMOTE MY OWE 

1153
00:49:47,065 --> 00:49:48,533
CARD I DIDN'T MEAN AND THEN THE 

1154
00:49:48,533 --> 00:49:51,869
CONTROLS.  AND THEN IN SKELETAL 

1155
00:49:51,869 --> 00:49:52,570
MUSCLE. 

1156
00:49:52,570 --> 00:49:54,205
SO ANOTHER INTERESTING AGENT.  

1157
00:49:54,205 --> 00:49:59,977
AND, YOU KNOW, THIS WAS SORT OF 

1158
00:49:59,977 --> 00:50:01,412
AN ACCIDENT ONE OF OUR RESEARCH 

1159
00:50:01,412 --> 00:50:03,114
ASSISTANTS WAS STAINING, YOU 

1160
00:50:03,114 --> 00:50:09,387
KNOW, FOR CCR 2 AND NPRC FOR 

1161
00:50:09,387 --> 00:50:10,655
DIFFERENT PROJECTS AND USED 

1162
00:50:10,655 --> 00:50:13,324
ADJACENT PROJECTS FROM A 

1163
00:50:13,324 --> 00:50:13,958
BIOREPOSITORY.  AND WHAT'S KIND 

1164
00:50:13,958 --> 00:50:15,359
OF INTERESTING IS YOU CAN SEE 

1165
00:50:15,359 --> 00:50:18,329
THAT CCR 2 IS PRESENT ON 

1166
00:50:18,329 --> 00:50:20,264
DIFFERENT CELLS THAN NPRC AND WE

1167
00:50:20,264 --> 00:50:23,468
KNOW THIS, I MEAN, BY LITERATURE

1168
00:50:23,468 --> 00:50:28,539
CCR 2 IS PROTEESENT IN MONOCYTE 

1169
00:50:28,539 --> 00:50:30,108
BUT THESE ARE THE STAINED CELLS 

1170
00:50:30,108 --> 00:50:38,783
AND THE GREEN IS CCR 2.  AND IS 

1171
00:50:38,783 --> 00:50:42,920
THERE SOME UNEVENNESS IN THE 

1172
00:50:42,920 --> 00:50:43,921
STAINING HERE AND ONCE YOU GET 

1173
00:50:43,921 --> 00:50:47,125
TO THE ENDOTHELIUM THIS IS THE 

1174
00:50:47,125 --> 00:50:49,660
PRESENCE IN THE CELLS.  PRESENT 

1175
00:50:49,660 --> 00:50:51,829
IN VASCULAR SMOOTH MUSCLE CELLS,

1176
00:50:51,829 --> 00:50:56,434
IN MACROPHAGES AND ALSO IN THE 

1177
00:50:56,434 --> 00:50:58,769
ENDOTHELIUM.  NOW, ULTIMATELY, 

1178
00:50:58,769 --> 00:51:00,738
YOU KNOW, WHAT MIGHT BE -- IF I 

1179
00:51:00,738 --> 00:51:02,573
LIVE LONG ENOUGH, WHAT WOULD BE 

1180
00:51:02,573 --> 00:51:05,643
OUR ULTIMATE GOAL?  COULD YOU 

1181
00:51:05,643 --> 00:51:10,581
SUPPRESS NPRC AND SLOW DOWN 

1182
00:51:10,581 --> 00:51:11,349
ARTHROSCLEROSIS?  AND, YOU KNOW,

1183
00:51:11,349 --> 00:51:15,153
ONE QUESTION IS HOW WOULD YOU 

1184
00:51:15,153 --> 00:51:17,088
USE A NANOPARTICLE THAT MIGHT 

1185
00:51:17,088 --> 00:51:18,523
INVOLVE CARGO SWITCHING?  THIS 

1186
00:51:18,523 --> 00:51:20,224
WAS AN ARTICLE NOT WRITTEN BY US

1187
00:51:20,224 --> 00:51:24,362
BUT ONE THAT I THOUGHT WAS 

1188
00:51:24,362 --> 00:51:31,836
INSPIRATIONAL.  THEY HAVE A CORE

1189
00:51:31,836 --> 00:51:35,606
STRUCTURE AND THIS IS A COMPLEX.

1190
00:51:35,606 --> 00:51:38,409
AND THE SHELL IS PHOSPHOLIPIDS. 

1191
00:51:38,409 --> 00:51:41,546
AND WHEN THE CSNP ENCOUNTERS 

1192
00:51:41,546 --> 00:51:43,548
CHOLESTEROL THE STATINS RELEASE 

1193
00:51:43,548 --> 00:51:46,918
AND THE STATIN AND CHOLESTEROL 

1194
00:51:46,918 --> 00:51:48,452
SKA SKRENGED THROW THE 

1195
00:51:48,452 --> 00:51:48,853
CARGO-SWITCHING.  

1196
00:51:48,853 --> 00:51:51,656
SO ARE THERE THINGS THAT COULD 

1197
00:51:51,656 --> 00:51:54,058
BE DONE, COULD BE PLACED ON A 

1198
00:51:54,058 --> 00:51:57,261
NANOPARTICLE WITH THIS C TYPE, 

1199
00:51:57,261 --> 00:51:59,397
THIS CNF THAT'S TARGETING THE 

1200
00:51:59,397 --> 00:52:04,769
PEPTIDE RECEPTOR THAT MIGHT SLOW

1201
00:52:04,769 --> 00:52:05,570
DOWN THE ARTHROSCLEROSIS.  SO 

1202
00:52:05,570 --> 00:52:07,505
UNDERSTANDING PLAQUE BIOLOGY AND

1203
00:52:07,505 --> 00:52:09,373
IMAGING IT ON THE PATIENT LEVEL 

1204
00:52:09,373 --> 00:52:11,442
AND BEING ABLE TO IMAGE IT CAN 

1205
00:52:11,442 --> 00:52:14,946
HELP US UNDERSTAND, YOU KNOW, 

1206
00:52:14,946 --> 00:52:16,681
WHICH PLAQUES RUPTURE, IT 

1207
00:52:16,681 --> 00:52:19,984
MIGHT -- WHICH ONES MIGHT CAUSE 

1208
00:52:19,984 --> 00:52:21,652
MAJOR AVERSE EVENT AND WHO YOU 

1209
00:52:21,652 --> 00:52:23,421
MIGHT BE ABLE TO INTERVENE ON 

1210
00:52:23,421 --> 00:52:27,525
AND WHAT WE'RE SEEING AT THE 

1211
00:52:27,525 --> 00:52:31,462
MOLECULAR LEVEL.  SO, YOU KNOW, 

1212
00:52:31,462 --> 00:52:32,096
FURTHERING PRECISION MEDICINE 

1213
00:52:32,096 --> 00:52:33,764
THERAPY.  NOW I DID PROMISE YOU,

1214
00:52:33,764 --> 00:52:40,304
HOW AM I DOING ON TIME HERE?  

1215
00:52:40,304 --> 00:52:42,240
I'VE GOT A FEW MORE MINUTES.  

1216
00:52:42,240 --> 00:52:46,043
GOOD.  WHAT DO YOU NEED GET ALL 

1217
00:52:46,043 --> 00:52:48,913
THIS IN, THE AGENTS LIKE THIS 

1218
00:52:48,913 --> 00:52:50,715
THROUGH THE FDA INTO HUMANS YOU 

1219
00:52:50,715 --> 00:52:51,949
NEED A LOT OF PEOPLE IT'S 

1220
00:52:51,949 --> 00:52:56,087
HELPFUL TO GET ADVICE.  THIS IS 

1221
00:52:56,087 --> 00:52:57,755
OUR SYNTHESIS CHEMISTS GROUP AND

1222
00:52:57,755 --> 00:53:00,658
HERE IS SALLY, AS I MENTIONED 

1223
00:53:00,658 --> 00:53:03,361
WAS A RADIO PHARMACIST WHO 

1224
00:53:03,361 --> 00:53:04,595
REALLY HAS A STRONG 

1225
00:53:04,595 --> 00:53:07,798
UNDERSTANDING OF THE FDA, SHE'S 

1226
00:53:07,798 --> 00:53:09,667
NOW EMERITUS, SHE'S NOW AN 

1227
00:53:09,667 --> 00:53:11,636
EMERITUS PROFESSOR AND MIKE 

1228
00:53:11,636 --> 00:53:15,006
NICKELS IS THE DIRECTOR OF OUR 

1229
00:53:15,006 --> 00:53:16,741
CYCLOTRON CENTER AND THEN, YOU 

1230
00:53:16,741 --> 00:53:18,242
KNOW, DESPITE WHAT I SAID I 

1231
00:53:18,242 --> 00:53:23,347
THINK IT IS A GOOD IDEA TO GET 

1232
00:53:23,347 --> 00:53:25,216
PRE-IND ADVICE.  THEY'RE USUALLY

1233
00:53:25,216 --> 00:53:26,751
VERY FORTHCOMING.  SOMETIMES 

1234
00:53:26,751 --> 00:53:28,386
THEY'LL EVEN DO IT JUST BY 

1235
00:53:28,386 --> 00:53:29,587
E-MAIL.  YOU CAN ASK YOUR 

1236
00:53:29,587 --> 00:53:32,757
QUESTION AND THEN THEY WILL 

1237
00:53:32,757 --> 00:53:35,159
RESPOND.  AND SINCE THAT FIRST, 

1238
00:53:35,159 --> 00:53:37,194
THE BEGINNING, WE'VE DONE THAT 

1239
00:53:37,194 --> 00:53:38,629
AND BEEN VERY SUCCESSFUL IN 

1240
00:53:38,629 --> 00:53:40,097
GETTING ADVICE FROM THE NIH EVEN

1241
00:53:40,097 --> 00:53:43,934
JUST BY E-MAIL.  SO THE LESSONS 

1242
00:53:43,934 --> 00:53:45,636
LEARNED ARE, YOU KNOW, HAVE A 

1243
00:53:45,636 --> 00:53:46,671
STRONG INFRASTRUCTURE, HAVE A 

1244
00:53:46,671 --> 00:53:48,205
STRONG AND DIVERSE TEAM, YOU 

1245
00:53:48,205 --> 00:53:50,341
WANT TO GET ADVICE, YOU WANT TO 

1246
00:53:50,341 --> 00:53:53,644
HAVE A GOOD INDICATION AND A 

1247
00:53:53,644 --> 00:53:55,413
MEANINGFUL TARGET.  HAVE STRONG 

1248
00:53:55,413 --> 00:53:56,047
PRELIMINARY DATA.  BE PREPARED 

1249
00:53:56,047 --> 00:53:58,482
TO WRITE A LOT OF SOPS AND THEN 

1250
00:53:58,482 --> 00:53:59,817
GIVE YOURSELF TIME, YOU KNOW, IF

1251
00:53:59,817 --> 00:54:02,953
YOU'RE PLANNING TO PUT IN AN R 

1252
00:54:02,953 --> 00:54:04,388
01, START THE YEAR BEFORE, DOING

1253
00:54:04,388 --> 00:54:07,458
A LOT OF THE STUFF.  MAYBE EVEN 

1254
00:54:07,458 --> 00:54:09,527
A YEAR AND A HALF BEFORE.  AND 

1255
00:54:09,527 --> 00:54:13,230
THEN HOW DO WE ENCOURAGE PEOPLE 

1256
00:54:13,230 --> 00:54:15,833
WHO START OFF WITH INTERESTING 

1257
00:54:15,833 --> 00:54:17,201
IDEAS AND ENTHUSIASM FOR 

1258
00:54:17,201 --> 00:54:18,336
RESEARCH.  ONE OF THE QUESTIONS 

1259
00:54:18,336 --> 00:54:20,271
IS WHY AM I STILL HERE DOING 

1260
00:54:20,271 --> 00:54:22,440
THIS INSTEAD OF OFF MAKING, YOU 

1261
00:54:22,440 --> 00:54:24,809
KNOW, HUNDREDS OF THOUSANDS OF 

1262
00:54:24,809 --> 00:54:27,011
DOLLARS?  BUT THIS WAS ME IN 

1263
00:54:27,011 --> 00:54:28,312
MEDICAL SCHOOL AND THIS WAS IN 

1264
00:54:28,312 --> 00:54:30,815
THE 80S SO YOU NOTICE THE, WHAT 

1265
00:54:30,815 --> 00:54:33,651
IS IT THE WINGED HAIR TYPE THING

1266
00:54:33,651 --> 00:54:36,554
AND THEN THIS IS ME ON THE NIH 

1267
00:54:36,554 --> 00:54:40,091
CAMPUS AND THIS IS BUILDING 37 I

1268
00:54:40,091 --> 00:54:41,425
THINK.  SO, AT DUKE WE HAD TO DO

1269
00:54:41,425 --> 00:54:44,128
A YEAR OF RESEARCH IN MEDICAL 

1270
00:54:44,128 --> 00:54:48,265
SCHOOL AND I HAD A GRANT WITH --

1271
00:54:48,265 --> 00:54:49,667
A MEDICAL STUDENT GRANT AT WASH 

1272
00:54:49,667 --> 00:54:52,370
U BUT I WAS DATING ANOTHER 

1273
00:54:52,370 --> 00:54:55,373
FELLOW CLASSMATE WHO HAD A 

1274
00:54:55,373 --> 00:54:57,641
GRANT -- A HOWARD HUGHES GRANT 

1275
00:54:57,641 --> 00:54:59,443
AND WAS LIVING IN THE CLOISTER 

1276
00:54:59,443 --> 00:55:04,115
SO, YOU KNOW, A LOT OF US AT THE

1277
00:55:04,115 --> 00:55:05,116
TIME WERE VERY INTERESTED IN THE

1278
00:55:05,116 --> 00:55:09,153
RESEARCH.  THIS IS A PICTURE OF 

1279
00:55:09,153 --> 00:55:11,355
KEENE AND THEN ANOTHER WHO 

1280
00:55:11,355 --> 00:55:12,556
CONVINCED ME TO GO INTO 

1281
00:55:12,556 --> 00:55:15,226
RADIOLOGY AND THEN I COULD DO 

1282
00:55:15,226 --> 00:55:19,530
RESEARCH ANDOLOGY  RADIOLOGY 

1283
00:55:19,530 --> 00:55:21,565
TOGETHER.  CHARLIE WAS IN 

1284
00:55:21,565 --> 00:55:23,601
RADIOLOGY BUT ALSO DOUBLE 

1285
00:55:23,601 --> 00:55:25,336
BOARDED IN INTERNAL MEDICINE AND

1286
00:55:25,336 --> 00:55:29,340
ONE WHO PREVAILED UPON HAROLD TO

1287
00:55:29,340 --> 00:55:33,644
ESTABLISH THE NIBIB.  

1288
00:55:33,644 --> 00:55:35,813
SO AT WASHINGTON UNIVERSITY IN 

1289
00:55:35,813 --> 00:55:37,648
OUR DEPARTMENT, WE HAVE THREE 

1290
00:55:37,648 --> 00:55:41,886
NIH FUNDED T32 PROGRAMS THROUGH 

1291
00:55:41,886 --> 00:55:44,355
THE NIV AND THEY'VE BEEN QUITE 

1292
00:55:44,355 --> 00:55:47,525
INSTRUMENTAL I THINK IN, YOU 

1293
00:55:47,525 --> 00:55:52,396
KNOW, KEEPING THE VISIBILITY OF 

1294
00:55:52,396 --> 00:55:52,930
RESEARCH PRESENT TO OUR 

1295
00:55:52,930 --> 00:55:54,432
CLINICIAN SCIENTISTS ESPECIALLY.

1296
00:55:54,432 --> 00:55:56,333
BUT ALSO THROUGHOUT THE 

1297
00:55:56,333 --> 00:55:57,968
DEPARTMENT.  AND THE FIRST ONE 

1298
00:55:57,968 --> 00:56:03,374
IS OPPORTUNITIES AND 

1299
00:56:03,374 --> 00:56:05,509
TRANSLATIONAL IMAGING, THESE ARE

1300
00:56:05,509 --> 00:56:07,445
FOR RESIDENTS AND FOR FELLOWS SO

1301
00:56:07,445 --> 00:56:09,280
HAVE AN M.D. SOME OF THEM MIGHT 

1302
00:56:09,280 --> 00:56:12,016
HAVE A PH.D. AS WELL.  BUT 

1303
00:56:12,016 --> 00:56:14,618
REALLY ALLOWING OUR RESIDENTS 

1304
00:56:14,618 --> 00:56:16,687
AND FELLOWS TO SEE RESEARCH, 

1305
00:56:16,687 --> 00:56:17,455
THEY HAVE, ESPECIALLY IN THOSE 

1306
00:56:17,455 --> 00:56:20,257
WHO ARE NOT IN THIS PROGRAM, YOU

1307
00:56:20,257 --> 00:56:24,528
KNOW, THESE RESIDENTS PRESENT 

1308
00:56:24,528 --> 00:56:26,831
AND WE HAVE A SEMINAR RESEARCH 

1309
00:56:26,831 --> 00:56:28,799
SEMINAR EVERY YEAR SO ALL OF OUR

1310
00:56:28,799 --> 00:56:31,268
RESIDENT GOES TO THAT, SO WE 

1311
00:56:31,268 --> 00:56:33,137
HAVE PEOPLE DOING RESEARCH WHO 

1312
00:56:33,137 --> 00:56:35,206
ARE ENTHUSIASTIC AND HAVE 

1313
00:56:35,206 --> 00:56:35,539
MENTORS.  

1314
00:56:35,539 --> 00:56:36,974
AND WE HAVE A SEMINAR SERIES 

1315
00:56:36,974 --> 00:56:38,309
THAT KIND OF GOES ALONG WITH 

1316
00:56:38,309 --> 00:56:39,710
THAT.  I WILL SHOW YOU A LITTLE 

1317
00:56:39,710 --> 00:56:43,714
BIT OF THAT.  THE 21ST CENTURY 

1318
00:56:43,714 --> 00:56:45,649
IMAGING SCIENCES PROGRAM IS A 

1319
00:56:45,649 --> 00:56:47,985
PRECLINICAL -- A PRE-DOCTORAL 

1320
00:56:47,985 --> 00:56:49,653
PROGRAM. 

1321
00:56:49,653 --> 00:56:52,656
AND THIS SUPPORTS OUR -- WE HAVE

1322
00:56:52,656 --> 00:56:53,290
MULTIPLE DIFFERENT DEPARTMENTS 

1323
00:56:53,290 --> 00:56:55,493
THAT WE PARTNER WITH, SO 

1324
00:56:55,493 --> 00:56:57,628
ENGINEERING, THE SCHOOL OF 

1325
00:56:57,628 --> 00:56:59,296
ENGINEERING, THERE'S AN IMAGING 

1326
00:56:59,296 --> 00:57:00,931
SCIENCES PATHWAY, MANY OF THE 

1327
00:57:00,931 --> 00:57:02,433
STUDENTS COME IN FROM THAT, SOME

1328
00:57:02,433 --> 00:57:05,803
COME IN FROM DBBS, IT'S A 

1329
00:57:05,803 --> 00:57:07,505
DEVELOPMENTAL BIOLOGY PH.D. 

1330
00:57:07,505 --> 00:57:09,740
PROGRAM.  AND THEN THIRDLY, MOST

1331
00:57:09,740 --> 00:57:12,510
RECENTLY, THIS WAS A T32 

1332
00:57:12,510 --> 00:57:13,944
OBTAINED A COUPLE OF YEARS AGO. 

1333
00:57:13,944 --> 00:57:15,946
THIS ONE'S ACTUALLY THROUGH THE 

1334
00:57:15,946 --> 00:57:19,149
NCI AND IT'S A TRANSLATIONAL 

1335
00:57:19,149 --> 00:57:20,050
IMAGING AND PHARMACEUTICAL 

1336
00:57:20,050 --> 00:57:25,623
SCIENCES T32 AND IT TRAINS M.D.S

1337
00:57:25,623 --> 00:57:28,125
AND PH.D.S TO BE RADIO CHEMISTS 

1338
00:57:28,125 --> 00:57:30,027
AND REALLY TO TRANSLATE SOME OF 

1339
00:57:30,027 --> 00:57:33,264
THE RADIO TRACERS THAT I'VE 

1340
00:57:33,264 --> 00:57:34,665
TALKED ABOUT.  

1341
00:57:34,665 --> 00:57:37,668
SO THE T 32 PROGRAM TOP TIER, 

1342
00:57:37,668 --> 00:57:40,137
THE CLINICIAN SCIENTIST PROGRAM 

1343
00:57:40,137 --> 00:57:43,207
IS ONE OF SIX CLINICIAN 

1344
00:57:43,207 --> 00:57:45,576
SCIENTIST PROGRAMS IN THE 

1345
00:57:45,576 --> 00:57:45,843
COUNTRY. 

1346
00:57:45,843 --> 00:57:50,748
JOHNS HON  HOPKINS, SOUTHWESTERN

1347
00:57:50,748 --> 00:57:51,749
ALL HAVE THESE. 

1348
00:57:51,749 --> 00:57:56,153
AND I FEEL LIKE THERE ARE PLACES

1349
00:57:56,153 --> 00:57:58,122
TO HAVE THE CAPABILITY TO 

1350
00:57:58,122 --> 00:58:00,291
PROVIDE TRAINEES WITH RESEARCH 

1351
00:58:00,291 --> 00:58:01,659
AND TEACH THEM TO BECOME 

1352
00:58:01,659 --> 00:58:03,193
INDEPENDENT RESEARCHERS.  HERE 

1353
00:58:03,193 --> 00:58:05,663
ARE OUR PROGRAM DIRECTORS, I'M 

1354
00:58:05,663 --> 00:58:07,765
ONE OF THE PROGRAM DIRECTORS I'M

1355
00:58:07,765 --> 00:58:10,067
THE PRINCIPLE DIRECTOR AND THEN 

1356
00:58:10,067 --> 00:58:13,337
A COUPLE OF CO-PIS AND I THINK 

1357
00:58:13,337 --> 00:58:16,674
AS WE GO INTO OUR NEXT 

1358
00:58:16,674 --> 00:58:21,512
SUBMISSION, I WILL PROBABLY 

1359
00:58:21,512 --> 00:58:23,781
SWITCH OUT TO DR. LONG YOU ANN 

1360
00:58:23,781 --> 00:58:27,418
AND MAYBE STAY ON AS A CORKS PI,

1361
00:58:27,418 --> 00:58:29,186
RICHARD WAUL WAS OUR PREVIOUS 

1362
00:58:29,186 --> 00:58:29,420
CHAIR. 

1363
00:58:29,420 --> 00:58:30,854
AND THEN WE HAVE, THE PREVIOUS 

1364
00:58:30,854 --> 00:58:32,690
CHAIR OF THE DEPARTMENT.  WHICH 

1365
00:58:32,690 --> 00:58:33,490
I SHOULD SAY BECAUSE HE WAS THE 

1366
00:58:33,490 --> 00:58:35,726
ONE WHO SAID PAM, YOU SHOULD 

1367
00:58:35,726 --> 00:58:39,129
SUBMIT A T-32 SO HE WAS THE 

1368
00:58:39,129 --> 00:58:40,664
INSPIRATION BUT I SUBMITTED THE 

1369
00:58:40,664 --> 00:58:42,266
GRANT.  AND THEN WE HAVE 

1370
00:58:42,266 --> 00:58:45,569
RESEARCH RESIDENCY PROGRAM 

1371
00:58:45,569 --> 00:58:46,971
DIRECTORS DR. UP POE LEE TO, 

1372
00:58:46,971 --> 00:58:50,074
DR. RAH GEE, BOTH OF THESE 

1373
00:58:50,074 --> 00:58:51,108
INDIVIDUALS RUN THE RESEARCH 

1374
00:58:51,108 --> 00:58:53,611
RESIDENT PROGRAM AND WE'VE HAD A

1375
00:58:53,611 --> 00:58:56,847
SEPARATE NRMP NUMBER FOR OUR 

1376
00:58:56,847 --> 00:58:57,648
RESEARCH RESIDENT TRACK GOING 

1377
00:58:57,648 --> 00:59:02,419
BACK TO 1989 EVEN BEFORE THE 

1378
00:59:02,419 --> 00:59:04,355
LOCALMAN PATHWAY IF PEOPLE KNOW 

1379
00:59:04,355 --> 00:59:07,491
WHAT THAT IS WITH THE ABR. 

1380
00:59:07,491 --> 00:59:08,759
THE T32 PROGRAMS HAVE ELEVATED 

1381
00:59:08,759 --> 00:59:12,896
THE RESEARCH BECAUSE, YOU KNOW, 

1382
00:59:12,896 --> 00:59:14,498
IT -- THEY INSIST UPON THE 

1383
00:59:14,498 --> 00:59:16,100
INSTRUCTION OF THE RESEARCH 

1384
00:59:16,100 --> 00:59:16,734
RIGOR AND REPRODUCIBILITY AND 

1385
00:59:16,734 --> 00:59:21,672
THE ETHICS AND, YOU KNOW, AND 

1386
00:59:21,672 --> 00:59:24,241
THE DIDACTIC WHICH JUST I THINK,

1387
00:59:24,241 --> 00:59:28,412
YOU KNOW, ELEVATE THE VISIBILITY

1388
00:59:28,412 --> 00:59:31,515
AND THEN ALSO THE, YOU KNOW, THE

1389
00:59:31,515 --> 00:59:34,685
RIGOR OF THE RESEARCH SO THESE 

1390
00:59:34,685 --> 00:59:37,221
ARE THE PIS OF THE PROGRAM 

1391
00:59:37,221 --> 00:59:39,490
DIRECTORS FOR OUR TRANSLATIONAL 

1392
00:59:39,490 --> 00:59:41,625
IMAGING AND RADIO PHARMACEUTICAL

1393
00:59:41,625 --> 00:59:47,631
SCIENCES.  TAMMY BEN ZINGER, AND

1394
00:59:47,631 --> 00:59:49,667
WILL TU AND WE HAD THIS SUMMER 

1395
00:59:49,667 --> 00:59:51,969
STUDENT PROGRAM WHICH CAN BE AN 

1396
00:59:51,969 --> 00:59:54,338
ENTREE INTO SOME OF THESE T32S. 

1397
00:59:54,338 --> 00:59:56,507
WE HAVE PEOPLE WHO COME OVER THE

1398
00:59:56,507 --> 00:59:58,642
SUMMER.  WE GIVE THEM A STIPEND 

1399
00:59:58,642 --> 01:00:01,445
AND BRING IN, YOU KNOW, FIFTEEN 

1400
01:00:01,445 --> 01:00:04,515
OR SO STUDENTS.  MEDICAL 

1401
01:00:04,515 --> 01:00:05,783
STUDENTS.  FROM THROUGHOUT THE 

1402
01:00:05,783 --> 01:00:08,986
UNITED STATES IN TO DO RESEARCH 

1403
01:00:08,986 --> 01:00:13,557
WITH US.  HERE ARE SOME OF OUR 

1404
01:00:13,557 --> 01:00:14,291
CURRENT RESIDENTS AND FELLOWS.  

1405
01:00:14,291 --> 01:00:16,193
THIS YEAR WE HAD THREE OF THEM 

1406
01:00:16,193 --> 01:00:18,462
WHO RECEIVED, THESE ARE THREE 

1407
01:00:18,462 --> 01:00:20,864
RESIDENTS.  THEY'VE RECEIVED 

1408
01:00:20,864 --> 01:00:23,734
RSNA GRANTS.  AND THEN DAVID 

1409
01:00:23,734 --> 01:00:25,669
BALLARD IS A FORMER TRAINEE WHO 

1410
01:00:25,669 --> 01:00:28,072
IS NOW FACULTY WHO HAS RECEIVE 

1411
01:00:28,072 --> 01:00:33,310
AN RSNA RESEARCH SCHOLAR GRANT. 

1412
01:00:33,310 --> 01:00:35,713
SO YOU KNOW I THINK I WILL GO 

1413
01:00:35,713 --> 01:00:37,448
AHEAD AND STOP THERE.  IT'S BEEN

1414
01:00:37,448 --> 01:00:39,316
VERY EXCITING TO BE ABLE TO 

1415
01:00:39,316 --> 01:00:40,751
PROVIDE THIS EDUCATION TO OUR 

1416
01:00:40,751 --> 01:00:43,520
RESIDENTS AND TO OUR FELLOWS.  

1417
01:00:43,520 --> 01:00:45,055
AND I AM KIND OF HOPING THAT 

1418
01:00:45,055 --> 01:00:48,125
THERE'S A FUTURE FOR RESEARCH IN

1419
01:00:48,125 --> 01:00:49,460
IMAGING THAT NOT EVERYBODY GOES 

1420
01:00:49,460 --> 01:00:53,097
OFF INTO PRIVATE PRACTICE AND 

1421
01:00:53,097 --> 01:00:58,635
WANTS THOSE BUNNY SLIPPERS AND 

1422
01:00:58,635 --> 01:01:00,637
READING FOR HIGH REIMBURSEMENT 

1423
01:01:00,637 --> 01:01:02,206
IN THEIR HOMES.  SO, THANKS.

1424
01:01:02,206 --> 01:01:09,613
>> AUDIENCE: (APPLAUSE).

1425
01:01:09,613 --> 01:01:11,548
>> THANK YOU.  MUCH
APPRECIATED.

1426
01:01:11,548 --> 01:01:14,785
I HAD ASKED SOME OF THESE EXACT 

1427
01:01:14,785 --> 01:01:15,452
QUESTIONS AND THANK YOU SO MUCH 

1428
01:01:15,452 --> 01:01:17,387
FOR TELLING US WHAT YOU'RE DOING

1429
01:01:17,387 --> 01:01:19,757
THERE.  I REALLY WANTED TO 

1430
01:01:19,757 --> 01:01:22,559
UNDERSTAND HOW TO KEEP PEOPLE IN

1431
01:01:22,559 --> 01:01:24,161
THE RESEARCH FIELD AND NOT GOING

1432
01:01:24,161 --> 01:01:26,563
TO THE BASEMENT IN BUNNY 

1433
01:01:26,563 --> 01:01:27,664
SLIPPERS.  WE CAN TAKE SOME 

1434
01:01:27,664 --> 01:01:28,665
QUESTIONS AND THEN THERE MAY BE 

1435
01:01:28,665 --> 01:01:37,641
SOME ONLINE AS WELL.

1436
01:01:37,641 --> 01:01:39,276
>> THANK YOU, PAM.  THAT
WAS 

1437
01:01:39,276 --> 01:01:41,578
REALLY GREAT.  AND NEXT TIME YOU

1438
01:01:41,578 --> 01:01:43,380
HAVE A SEANCE WITH MIKE, PLEASE 

1439
01:01:43,380 --> 01:01:44,681
INVITE US.  I'D LOVE TO BE 

1440
01:01:44,681 --> 01:01:44,882
THERE.

1441
01:01:44,882 --> 01:01:48,886
>> WE WILL.  I KNOW,
WONDER WITH

1442
01:01:48,886 --> 01:01:50,621
HIS ONLY IN THIS CASE SENSE IN 

1443
01:01:50,621 --> 01:01:52,022
THE AFTERLIFE WHAT HE WOULD BE 

1444
01:01:52,022 --> 01:01:54,792
ABLE TO TELL US E.

1445
01:01:54,792 --> 01:01:56,393
>> EXACTLY.  I WAS
THINKING HOW 

1446
01:01:56,393 --> 01:01:57,661
I WOULD APPROACH THIS PROBLEM 

1447
01:01:57,661 --> 01:01:59,062
AND I AM SO HAPPY I DON'T HAVE 

1448
01:01:59,062 --> 01:02:05,536
THE PROBLEM OF TRYING TO FIND A 

1449
01:02:05,536 --> 01:02:08,138
MILL MEET IR SIZED ARTERY ROW 

1450
01:02:08,138 --> 01:02:13,343
PLAQUE WHAT IS YOUR THINKING OF 

1451
01:02:13,343 --> 01:02:16,313
LOOKING FOR A LARGE PARTICLE.  

1452
01:02:16,313 --> 01:02:18,315
22 NANOMETERS WHICH WOULD HAVE A

1453
01:02:18,315 --> 01:02:19,616
RELATIVELY LONG CLEARANCE TIME 

1454
01:02:19,616 --> 01:02:21,118
FROM THE LUMEN?  I WOULD THINK 

1455
01:02:21,118 --> 01:02:22,686
YOU WOULD WANT TO GET IT OUT OF 

1456
01:02:22,686 --> 01:02:25,189
THE LUMEN AS QUICKLY AS 

1457
01:02:25,189 --> 01:02:26,123
POSSIBLE.  SO I'M CURIOUS ABOUT 

1458
01:02:26,123 --> 01:02:28,158
THAT AND THAT MUST HAVE DRIVEN 

1459
01:02:28,158 --> 01:02:29,660
THE CHOICE OF COPPER TO BE 

1460
01:02:29,660 --> 01:02:32,062
SLIGHTLY LONGER LIVED.  AND THEN

1461
01:02:32,062 --> 01:02:34,431
SO WHEN DO YOU ACTUALLY IMAGE 

1462
01:02:34,431 --> 01:02:35,966
THE PATIENT AFTER INJECTION?

1463
01:02:35,966 --> 01:02:40,204
>> SO THAT'S TRUE, WITH
THE 

1464
01:02:40,204 --> 01:02:40,904
NANOPARTICLE, THIS PARTICULAR 

1465
01:02:40,904 --> 01:02:42,706
NANOPARTICLE AS I MENTIONED HAS 

1466
01:02:42,706 --> 01:02:46,310
THE PEG ARMS AND THAT KEEPS, 

1467
01:02:46,310 --> 01:02:48,312
DOES GIVE IT A LONG 

1468
01:02:48,312 --> 01:02:50,013
INTRAVASCULAR HALF LIFE AND, YOU

1469
01:02:50,013 --> 01:02:52,182
KNOW, EARLY ON WE DID LOOK AT 

1470
01:02:52,182 --> 01:02:55,319
JUST COPPER 64 AND THE PEPTIDE 

1471
01:02:55,319 --> 01:02:56,920
ITSELF.  THE NANOPARTICLE HAD 

1472
01:02:56,920 --> 01:02:59,489
TWO REASONS, ONE WAS THE LONGER 

1473
01:02:59,489 --> 01:03:00,791
INTRAVASCULAR HALF LIFE.  THE 

1474
01:03:00,791 --> 01:03:02,793
SECOND REASON WAS THE GRANT WE 

1475
01:03:02,793 --> 01:03:04,661
WERE APPLYING FOR WAS A NANO 

1476
01:03:04,661 --> 01:03:06,263
IMAGING GRANT.  AND SO WE WERE 

1477
01:03:06,263 --> 01:03:09,199
LIKE WE BETTER PUT A 

1478
01:03:09,199 --> 01:03:11,368
NANOPARTICLE ON THIS.  BUT, YOU 

1479
01:03:11,368 --> 01:03:13,237
KNOW, THE DISADVANTAGE IS THAT 

1480
01:03:13,237 --> 01:03:15,305
YOU HAVE TO INJECT AND THEN YOU 

1481
01:03:15,305 --> 01:03:18,942
IMAGE TWELVE HOURS LATER.  12-18

1482
01:03:18,942 --> 01:03:20,577
SO BASICALLY WE BRING THE 

1483
01:03:20,577 --> 01:03:24,014
PATIENTS IN IN THE AFTERNOON, WE

1484
01:03:24,014 --> 01:03:24,882
INJECT AROUND 3 O'CLOCK AND THEN

1485
01:03:24,882 --> 01:03:27,451
WE PUT THEM UP IN, YOU KNOW, A 

1486
01:03:27,451 --> 01:03:28,652
HOTEL RIGHT NEXT DOOR AND THEN 

1487
01:03:28,652 --> 01:03:31,922
THEY COME BACK IN AT 7:00 IN THE

1488
01:03:31,922 --> 01:03:33,390
MORNING AND WE IMAGE THEM.  IF 

1489
01:03:33,390 --> 01:03:35,192
YOU'RE DOING THIS, NOWADAYS, 

1490
01:03:35,192 --> 01:03:37,127
PATIENTS WANT THINGS THAT ARE 

1491
01:03:37,127 --> 01:03:37,928
REALLY EFFICIENT.  AND SO, 

1492
01:03:37,928 --> 01:03:41,632
ANOTHER REASON FOR LOOKING AT 

1493
01:03:41,632 --> 01:03:44,401
OTHER NANOPARTICLES LIKE GOLD OR

1494
01:03:44,401 --> 01:03:46,670
MAYBE WE WERE CONSIDERING WITH 

1495
01:03:46,670 --> 01:03:49,072
THE DIFFERENT CONJUGATE DO I 

1496
01:03:49,072 --> 01:03:53,477
WANT TO GO WITH CNF AND COPPER 

1497
01:03:53,477 --> 01:03:56,213
64 AGAIN.  AND TRY TO SEE IF WE 

1498
01:03:56,213 --> 01:03:57,214
CAN SHORTEN THAT WINDOW.  SO 

1499
01:03:57,214 --> 01:03:58,482
THAT YOU KNOW, YOU COULD IMAGE 

1500
01:03:58,482 --> 01:04:01,618
AND HAVE A SHORTER UPTAKE TIME. 

1501
01:04:01,618 --> 01:04:04,388
AND, YOU KNOW, SO THAT IS A 

1502
01:04:04,388 --> 01:04:07,557
DISADVANTAGE.  AND I THINK IT'S 

1503
01:04:07,557 --> 01:04:08,959
ACTUALLY HINDERED SOME OF THE --

1504
01:04:08,959 --> 01:04:10,661
WE'VE HAD SOME VENTURE 

1505
01:04:10,661 --> 01:04:12,429
CAPITALISTS WHO HAVE BEEN 

1506
01:04:12,429 --> 01:04:13,130
INTERESTED IN THEIR KIND OF 

1507
01:04:13,130 --> 01:04:14,331
LIKE, YOU HAVE TO COME BACK THE 

1508
01:04:14,331 --> 01:04:21,638
NEXT MORNING.  SO THAT IS A 

1509
01:04:21,638 --> 01:04:31,148
DISADVANTAGE.  THANK YOU VERY 

1510
01:04:31,148 --> 01:04:41,658
MUCH.  DELIGHTED TO BE HERE.