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ALL RIGHT, I'M ELIZABETH
JONES, CHIEF OF RADIOLOGY AND
IMAMILLIOING SCIENCES AT THE
CLINICAL TRUSTEES AND I WANT TO
WELCOME YOU TO THE ANNUAL JOHN
DOPPMAN MEMORIAL LECTURE AND
IMAGING SCIENCES.
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OF THE PRESENTATION.
THIS LECTURE HONORS THE MEMORY
OF DR. JOHN DOPPMAN, WHO WAS A
SKILLED RADIOLOGIST AND CHAIR OF
THE RADIO LOGICAL DEPARTMENT OF
THE CLINICAL CENTER.
HE WAS HERE FOR 36 YEARS.
THOSE OF US WHO ANYHOW HIM KNEW
HIM TO BE A COMPASSION AT
PHYSICIAN, ENTHUSIASTIC TEACHER
AND PILLAR OF THE RESEARCH
COMMUNITY HERE AT NE H.
I AM ALSO PLEASED TO WELCOME
MISS ANN MARIE DOPPMAN AND
DR. DOPPMAN'S FAMILY WHO ARE
JOINING US TODAY FOR THE LECTURE
BY VIDEOCAST.
TODAY WE ARE HONORED TO HAVE
DR. MARTIN POMPER, PROFESSOR OF
RADIOLOGY AND ASSOCIATE DEAN FOR
ENTREPRENEUR HELP AND TECHNOLOGY
DEVELOP AM AT THE JOHNS HOPKINS
MEDICAL SCHOOL.
DR. POMPER IS ON IN LECULAR
RESEARCH, HIS FOCUS ON NEW IMAGE
XG THERAPEUTIC AGENTS FOR
CANCER, CNS SYSTEM DISEASE AND
OTHER DISORDERS.
DR. POMPER EARNED HIS BACHELOR'S
DEGREE, Ph.D. AND MEDICAL
DEGREE FROM THE UNIVERSITY OF
ILLINOIS AT URBANACHAMPAGNE.
HE COMPLETED HIS INTERN HELP AT
JOHNS HOPKINS MEDICAL SCHOOL
WHERE HE ALSO COMPLOATED
RESIDENCYS IN BIOLOGY AND
RADIOLOGY, HE'S BEEN ON THE JOHN
HOPKINS SCHOOL OF MEDICINE SINCE
1995.
TODAY HE SERVES AS THE HENRY N.
PROFESSOR OF NUCLEAR MEDICINE
AND DIRECTOR OF THE DIVISION OF
NUCLEAR MEDICINE.
HE ALSO DIRECTS THE JOHNS
HOPKINS CENTER FOR TRANSLATIONAL
MOLECULAR IMAGING, CO-DIRECTS
FUNCTIONAL AND MOLECULAR IMAGING
PROGRAM AND CANCER IMAMILLIOING
CORE AND SERVES AS A CHIEF OF
THE MOLECULAR IMAGING RESEARCH
AMONG OTHER APPOINTMENTS.
DR. POMPER IS ALSO THE CREATOR
OR CO CREATOR OF MORE THAN 60
PATENT-PENDING INVENTIONS AND IN
THE PAST 15 YEARS HE HAS
CONFOUNDED 6 START-AUTOPSIES.
HE RECEIVED NUMEROUS AWARDS FOR
HIS WORK AS AN INVESTIGATOR,
PHYSICIAN AND TEACHER AND
ELECTED TO THE NAGGAL ACADEMY OF
INVENTORS IN 2016.
AND THE NATIONAL ACADEMY OF
MEDICINE IN 2017.
THIS YEAR HE WAS ELECTED AS THE
FELL OVERLAPPING OF SOCIETY OF
NUCLEAR MEDICINE CAN MODEL
CITIZEN LEAKULAR IMAGING AND
AWARDED THE INNOVATION PRIZE BY
THE INTERNATIONAL SOCIETY FOR
STRATEGIC STUDIES IN RADIOLOGY.
DR. POMPER WILL SPEAK ON
MOLECULAR IMAGING FOR LIFE,
PLEASE JOIN ME IN WELCOMING OUR
SPEAKER.
NWELL, THANK YOU FOR THE ULTRA
KIND INTRODUCTION.
SO YES, MOLECULAR IMANNUALING
FOR LIFE, THIS IS SORT OF MY
LIFE'S WORK AND IT'S A
TREMENDOUS HONOR TO BE HERE, I
REALLY ALWAYS ENJOY COMING DOWN
TO THE NIH LAST TIME I WAS HERE
AND I SPOKE IN THIS ROOM BUT THE
PODIUM WAS OVER THERE, I
REMEMBER AND IN ANY EVENT, I
DON'T HAVE IT ON THE
ACKNOWLEDGMENT SLIDE BUT ALMOST
ALL THE WORK I'LL DISCUSS WAS
FUNDED BY THE NIH, SO IT'S VERY
IMPORTANT THAT THE BUDGET AT
LEAST KEEPS UP WITH INFLATION.
SO I HOPE THAT WE DON'T HAVE TO
LIVE ON CONTINUING RESOLUTIONS
BUT THAT SEEMS TO BE HOW IT'S
BEEN.
SO I ACTUALLY KNEW DR. DOPPMAN,
I DIDN'T KNOW HIM WELL, BUT I
MET HIM A COUPLE TIMES WHEN I
WAS A TRAINEE AND IN MY EARLY
YEARS ON THE FACULTY,
DR. DOPPMAN EVEN THEN WHEN HE
WAS IN THE MID90S, HE WAS JUST
TREMENDOUSLY ENERGETIC AND VERY
POSITIVE AND A VERY KIND PERSON
WAS MY IMPRESSION.
AS WE ALL KNOW HE'S AN
INTERVENTIONAL RADIOLOGIST, HE
WAS HERE FOR MANY YEARS,
UNUSUALLY PROLIFIC IF YOU LOOK
AT HIS RECORD, HE HAD ALL SORTS
OF AWARDS, NIH DIRECTOR'S AWARD
AMONG OTHERS AND BASICALLY I
THINK MOST PEOPLE WILL DESCRIBE
HIM AS A FORCE OF NATURE.
ONCE IN A WHILE YOU SEE THESE
FORCES OF NATURE THAT JUST DON'T
STOP, THEY HAVE THEIR AGENDA AND
HE WAS 1 OF THOSE AND HE'S THE
REASON THAT THE NIH HAS DONE SO
INCREDIBLY WELL IN IMAGING AND
WAS A FORERUNNER IN ALWAYS ON
THE CUTTING EDGE OF WHAT WAS
HAPPENING IN IMAGING SINCE THE
MID60S.
SO, ALL RIGHT, SO HERE'S THE
OUTLINE.
I WILL TALK ABOUT PARADIGM
SHIFTS GOING ON IN MEDICINE AND
PRECISION MEDICINE.
YOU CAN GIVE AN EXAMPLE FOR OUR
WORK IN ANTIGEN TARGETING AND
TALKED ABOUT THERANOOF THETICS
WHICH IS NEW BUT OLD AS I WILL
SHOW AND DPIF A PERSPECTIVE AT
THE END, SO I THINK WE CAN ALL
AGREE THAT DAY-TO-DAY, YOU CAN
TELL IN THE CLINIC THAT TIMES
ARE DEFINITELY CHANGING EMPLOY
SO THIS OF COURSE IS
DR. HOUNDSFIELD AND HIS CT
SCANNER ISSUES THIS WAS A
PARADIGM SHIFT NOT ONLY IN
HIMMAGING BUT MEDICINE.
FOR THE FIRST TIME WE COULD SEE
CLEARLY WITHIN A PATIENT'S
NONINVASIVELY EMPLOY THIS WAS A
MASSIVE CHANGE, NOBEL PRIZE
WINNING DISCOVERY, CROSS
SECTIONAL IMANNUALING BUT I
THINK NOW, WHAT'S HAPPENING IN
2023, THAT MAKE HIS DISCOVERY
ALMOST LOOK MINOR TO A CERTAIN
EXTENT.
WE'RE BEGENERATEDDING TO APPLY
THESE PRECISION TECHNIQUES AND
CARE AND WE'RE ALSO BEGINNING TO
KEEP PEOPLE HEALTHY.
SO WE'RE IMPLEMENTING VALUE
BASED MEDICINE, PARTICULARLY
HERE IN THE STATE OF MARYLAND
FOR REASONS I WON'T DISCUSS BUT
THESE ARE HUGE PARADIGM SHIFTS.
SO TO SEE SOMETHING ON A SIMILAR
SCALE, I THINK WE HAVE TO GO
BACK TO 1930 WHERE MEDICAL
EDUCATION WAS BASICALLY SET UP
IN THE UNITED STATES WHERE
SCIENCE WAS FIRST SYSTEMATICALLY
BEING APPLIED TO MEDICAL
EDUCATION AND MEDICINE.
I THINK THAT'S THE KIND OF
CHANGE THAT WE'RE SEEING NOW FOR
REASONS THAT I WILL DISCUSS.
ONE OF THE BIG 1S IS PRECISION
EMPLOY SO PRECISION MEDICINE
WHEN WE THINK OF THAT, WE THINK
OF IT OFTEN AS A GENETIC
PHENOMENA THAT THE PATIENT'S
GENOME OR EPIGENOME DICTATES
WHAT KIND OF THERAPY THEY MIGHT
HAVE, BUT I THINK THAT THAT
REALLY IS MORE OR LESS JUST ON
THE GROUND INTELIENCE ABOUT THE
PATIENT WHEREAS WITH IMAGING WE
WITH BUILD THESE GUIDED MISSILES
WHERE WE MAKE PRECISION MEDICINE
ACTIONABLE BY FINDING AND
TARGETING DISEASE, VERY
SPECIFICALLY LEVERAGING THAT
GENETIC AND OTHER INFORMATION
ABOUT THE PATIENTS.
SO AS AN EXAMPLE AND I WILL
FOCUS ON CANCER IN THIS TALK BUT
I WILL SHOW A SLIDE HERE FROM
CENTRAL NERVOUS SYSTEM WORK THAT
WE'VE DONE, SO HERE WE HAVE 2
PATIENTS THAT COME INTO THE
EMERGENCY ROOM, YOUNG PATIENTS
SO THEY DON'T REALLY HAVE
MEDICAL RECORD THAT YOU COULD
LOOK AT BUT 1 HAS AFFECTIVE
PSYCHOSIS OR DEPRESSION, THE
OTHER 1 HAS NONAFFECTIVE
PSYCHOSIS OR SCETS FRENNIA BUT
WHEN THEY SHOW UP, THEY HAVE THE
SAME PHENOTYPE.
THEY'RE BOTH JUST PSYCHOTIC, SO
HOW ARE YOU GOING TO DETERMINE
HOW TO MANAGE THESE PATIENTS.
SO IT TURNS OUT THAT BY LOOKING
AT A VERY SPECIFIC TARGET IN THE
BRAIN, THE ALPHA NICK O TYPIC
RECEPTOR, WE FIND THAT PATIENTS
WITH SCHIZOPHRENIA ACTUALLY HAVE
MUCH LOWER BINDING.
WE DON'T KNOW WHY THAT IS, WE
KNOW IT'S NOT BECAUSE OF VARIOUS
MEDICATIONS, ET CETERA BUT WE
DON'T REALLY KNOW WHY THAT IS
AND WE'RE HOPEFULLY GOING TO
LOOK INTO THAT, OTHERS AND WE
ARE GOING TO LOOK INTO THAT, BUT
THE POINT IS THAT WE COULD TELL
WITH 1 SCAN IN A PATIENT, WE
COULD SUBTYPE THEM BO A
DIFFERENT TREATMENT GROUP.
THEY'RE GOING TO HAVE A MUCH
DIFFERENT JOURNEY WITH THEIR
ILLNESS AND THEY WOULD OTHERWISE
AND THAT'S REALLY WHAT WE TRY DO
WITH PRECISION IMAGING.
IT'S ABOUT TAKING PATIENTS WITH
SIMILAR PHENOTYPES AND SUBTYPING
THEM.
ANOTHER EXAMPLE, IS USING THIS
IMAGING AGENT FOR PROSTATE
CANCER, PYL, WE ARE 2 PATIENTS.
THEY GO TO THE PRIMARY CARE
PHYSICIAN, PHYSICIAN FEELS A
NODULE ON RECTAL EXAM, THEY HAVE
BIOPSIES, THE BIOPSIES SAY THEY
HAVE FLEECEON 9 PROSTATE CANCER
SO REALLY THE PHENOTYPES ARE
IDENTICAL UNTIL YOU USE A VERY
SPECIFIC IMAGING AGENT LIKE THIS
AND YOU CAN SEE THAT PATIENT A
HAS LOCALIZED DISEASE, PATIENT B
ALREADY HAS METASTATIC DISEASE
SO THEY'RE GOING TO ARE A VERY
DIFFERENT JOURNEYS.
SO HERE IS WHAT WE'RE HOPING TO
DO IN THE FUTURE WITH ALL OF OUR
MOLECULAR IMAGING THAT WE CAN
SUBTYPE PATIENTS AND GET THEM
EXACTLY THE KIND OF THERAPY THAT
THEY NEED.
SO WHEN WE TALK ABOUT IMAGING,
WE THINK ABOUT HOW IT DECREASES
MORTALITY THROUGH SCREEN,
DECREASES COST BY EARLY
DIAGNOSIS, AND DECREASING
CHANCES OF SURGERY AND
THERAPEUTIC CARE AND MONITORING
BUT THESE ARE CONVENTIONAL WAYS
ABOUT THINKING ABOUT IMAGING AND
I COULD SHOW THIS SLIDE 20 YEARS
AGO, SAME THING BUT WHAT'S
HAPPENING NOW?
WHERE DO I EMPHASIZE WE HAVE
THESE PARADIGM SHIFTS THAT ARE
OCCURRING IN WELL IF WE THINK
ABOUT NEXT GENERATION OR
PRECISION IMAGING NOW IN 2023,
WE HAVE PROTEIN COMPLEXIO
GENOMICS FOR IDENTIFYING TARGETS
TO LOOK AT IN PATIENTS, WE
DIDN'T HAVE THAT A FEW YEARS
AGO, EVEN.
WE HAD NEW WAYS OF GENERATING
AFFINITY PROBES TO THOSE
TARGETS, THERE'S ALL SORTS OF
POSSIBILITIES.
THERE'S EASIER WAYS TO MAKE
SMALL MOLECULES, CLICK SO CALLED
CLICK CHEMISTRY, THERE WAS NO
CLICK CHEMISTRY WHEN I WAS IN
GRAD SCHOOL AND 1 OF THE REASONS
THAT I WENT TO GRAD SCHOOL WAS
BECAUSE I WANTED TO USE CHEMICAL
APPROACHES TO THESE KINDS OF
PROBLEMS BUT NOW, THERE'S NOT
JUST ANTIBODIES BUT DIABODIES,
MINIBODIES, THERE'S DARKENS, ALL
SORTS OF DIFFERENT WAYS TO
ENGAGE BIOLOGICAL TARGETS, WE
ALSO HAVE AMAZINGLY RELEVANT
ANIMAL MODELS, GENETIC MODELS OF
DISEASE, WE HAVE NEW EQUIPMENT
AMAZING NEW SCANNERS WE HAVE,
HIGH TENSATIVITY, WE DO
EVERYTHING ON THE INTERNET, MORE
OR LESS SO THESE ARE ALL BIG
ADVANCES BUT THE NUMBER 1
ADVANCE OF EVERYTHING THAT
REALLY HAS MADE THE DIFFERENCE
IN THE LAST, YOU KNOW BETWEEN 5
AND 10 YEARS IS THE FACT THAT
EVERYTHING WE DO, ALL THE
COAALATING, ANNOTATING,
ANALYZING AND UTILIZING IS DONE
THROUGH CLOUD COMPUTING AND
THAT'S WHAT HAS MADE AND IS
GOING TO MAKE THE DIFFERENCE IN
EVERYTHING THAT WE DO, RIGHT
FROM FIGURING OUT WHAT TARGETS
LOOK LIKE, THAT WE WANT TO DRUG
TO COMING UP WITH NEW PROTEINS
WHICH COULDN'T BE DONE ISSUES
JUST LITERALLY AIER AGO.
SO THAT'S WHAT I MEAN BY
PARADIGM SHIFT.
SO THE OTHER THING I WANT TO
MENTION FOR THOSE OF YOU FROM
RADIOLOGY THAT THE GREAT GIFT OF
WHAT WE DO IS THAT WE PROVIDE A
PATH TO CURE BY EARLIER
DETECTION, PARTICULARLY IN
CANCER WHERE THERE ARE AN
INCREASING NUMBER OF THERAPEUTIC
AGENTS.
SO THIS IS A PAPER WRITTEN BOO I
1 OF MY COLLABORATORS, BERT
FOGELSTEIN, IT HAS A COMPLICATED
TITLE BUT WHAT HE SAID IS THAT
ONLY A THIRD OF THE VARIANCE
RISK TISSUES AMONG CANCERS ARE
INHERIT THE PREDISPOSITIONS, THE
MAJORITY IS DO YOU TO BAD LUCK.
SO YOU USUALLY DON'T SEE PHRASES
LIKE BAD LUCK IN SCIENCE PAPERS
BUT WHEN BERT WRITES IT AND
BACKS IT UP WITH ALL SORTS OF
MATH AND VALIDATION, IT SOUNDED
GOOD TO ME BUT WHEN I SAW THAT,
WHAT THAT TELLS ME IS THAT
2/3RDS OF CANCER IS JUST BAD
LUCK SO NO MATTER HOW MUCH KALE
YOU EAT OR HOW MUCH TIME I SPEND
ON AN ELLIPTICAL, WHAT ARE YOU
GOING TO DO?
IT'S GOING TO HAPPEN.
SO WHAT BERT DOES IS HE
DEVELOPED THESE TESTS FOR
CIRCULATING TUMOR DNA TO CATCH
IT EARLY, SO EARLY DETECTION
BEFORE IT BECOMES METASTATIC SO
YOU BEING DO SOMETHING ABOUT IT.
IT TURNS OUT THAT WITH HIS
TECHNIQUE, HE NEEDED ABOUT
50 MILLION CELLS, TO BE ABLE TO
DETECT CIRCULATING TNA SO KEEP
THAT NUMBER IN MIND, 50 MILLION
BUT THE POINT IS, THIS IS WHEN
WE DO, WE DETECT THINGS AS EARLY
AS WE CAN.
SO LOOT ME GIVE YOU XCHS OF
THAT, SO FLUTA MATE.
SO I HAVE A LONG STANDING
INTEREST IN FLUTA MATE.
I DON'T KNOW WHAT YOU WERE DOING
IN 1987, BUT AT THAT TIME I WAS
FINISHING UP IMRAD SCHOOL AND I
WAS ASHES FRAYED I WOULD HAVE TO
START WRITING GRAND ANDS THAT
SORT OF THING AND SO I STARTED
THINK BEING PROJECTS AND SO 1
WAS FLUTA MATE AND I THOUGHT
TOCK ISOTOPITY WAS
BEHIND--TOXICITY WAS BEHIND
ALZHEIMERS AND OTHER DISEASES
AND SO I DID THAT AT UNIVERSITY
OF ILLINOIS AND THEN I HAD TO
FINISH GRAD SCHOOL AND I WENT TO
RESIDENCY AND I LOST TRACK OF
BEING ABLE ON DO THAT BUT ALMOST
10 YEARS LATER, NOW I'M ON THE
FACULTY AS ASSISTANT PROFESSOR
OF JOHNS HOPKINS AND I ALWAYS
HAD MY MIND ON DPLIEWT MATE AND
I SAW THIS PAPER IN 1996 THAT
SHOWED THAT THERE WAS AN ENZYME
INHIBITOR THAT WAS ABLE TO
PREVENT.
IT WAS ACTUALLY AN ALOE DACE
INHIBITOR THAT WORKED ON ROUGH
ATOM DUCK OF FLUTE MATE.
IFFY WOO COULD INLAGE THAT
ENZYME, THAT WE WOULD HAVE A
ENSEL -
-SENSE OF WHAT A PORTION OF
THE FLUTE MATE WAS DOING AND WE
COULD LEARN MORE ABOUT
ALZHEIMER'S DISEASE AND MAYBE
TRY TO TARGETING SYSTEM
THEATSYSTEM.
SO THEY HAD THESE FANTASTIC
INHIBITORS, 275 PICO MOLAR WHICH
IS WHAT YOU WANT FOR A NEW RADIO
TRACER BUT I HAD TO LIKE--I WAS
A NEURORADIOLOGIST WHO WAS VERY
BUSY.
AFTER THIS DEMA CAME ON AND SHE
WAS A FELLOW AND SHE WAS A BIG
HELP SO I COULD THINK MORE ABOUT
THIS KIND OF THING.
BUT IN THE SAME YEAR, SO I SAW
THAT PAPER IN REALTIME IN 1996
AND I ALSO SAW THIS PAPER AND I
LEARNED THAT PSMA, IS AN ENZYME
THAT LOOKS LIKE A NEUROPEPTIDE
ACE SO I WENT BACK AND LOOKEDDA
THIS THE AND IT'S THE SAME
ENZYME.
AND I WAS THRILLED BECAUSE THESE
COMPOUNDS THAT ARE SUCH HIGH
AFEIGNITY WERE VERY HYDROPHILIC
MUCH THEY WEREN'T GOING TO GET
ACROSS THE BLOOD BRAIN BARRIER,
SO I PIVOTED TO PROSTATE CANCER,
I JUST GAVE UP NEURORADIOLOGY
AND ALL THAT I SAID LET'S JUST
WORK ON PROSTATE CANCER AND THIS
CAME OUT OF JOE COILS LAB AT
JOHNS HOPKINS.
I THINK HE HAD JUST LEFT AT THAT
TIME.
AND I WANT TO MENTION ALSO THIS
WAS COMMUNICATED BY
SEYMOR KEDDY, HE WAS A MASSIVE
HERO WHEN I WAS IN GRAD SCHOOL
AND JUNIOR FACULTY BECAUSE HE IS
SORT OF BEHIND A LOT OF THE WORK
IN QUANTITATIVE REGIONAL
CEREBRAL BLOOD FLOW ANALYSIS AND
REALLY JUST AN AMAZING PERSON.
SO BACK THEN IN REALTIME THIS IS
A NEW INVESTIGATOR AWARD, YOU
COULD TELL IT WAS A LONG TIME
AGO.
I DECIDED YOU KNOW WHAT I WILL
PIVOT AND WORK ON PROSTATE
CANCER, THERE'S NO PROSTATE, YOU
KNOW BLOOD BARRIER SO WE CAN GET
THESE HIGH AFFINITY AGENTS
ACROSS AND SO I WROTE A--WHAT I
THOUGHT WAS A REALLY NICE
PROPOSAL AT THE TIME BACK IN THE
MID90S AND I GOT MY USUAL RESULT
AT THE TIME AND I THINK THIS WAS
THE FIRST YEAR THAT THE
DEPARTMENT OF DEFENSE HAD THESE
KIND OF AWARDS ACTUALLY 1997,
98, AND I THOUGHT IT WAS A GOOD
IDEA, APPLIED FOR GRANTS, NEVER
GOT FUNDED AND 1 OF THE REASONS
I WAS TOLD IS THAT WE ALREADY
HAVE ANTIBODIES, YOU KNOW WHAT
ARE YOU WASTING YOUR TIME,
THERE'S ANTIBODIES FOR THIS AND
I WANT TO GIVE A SHOUT OUT TO
GERALD MURPHY WHO DOESN'T GET A
LOT OF CREDIT.
HE IS THE--HE IS THE PARENT OF
PSMA.
HE IN 1987, 10 YEARS BEFORE I
READ THOSE ARTICLES HE DORPHED
PSMA AND HE DEVELOPED THE FIRST
ANTIBODIES AGAINST IT.
AND IN 1996, THERE WAS A WAY TO
IMAGE MSMA BASED ON ANTIBODIES
SO I HAD A LOT OF PEOPLE SAYING,
YOU KNOW WE ALREADY HAVE A WAY
TO LOOK AT IT.
THIS WAS AN INDIAN 1 LEVEL
ANTIBODY, AND FOR THOSE WHO ARE
NOT NUCLEAR MEDICINE
SPECIALISTS, I WILL POINT OUT
THE CANCER IS RIGHT HERE, SO
THERE'S A LOT OF CANCER THERE,
SO, I STILL, EVEN THEN WHEN I
SAW THIS I SAID COME ON.
WE CAN DO BETTER THAN THAT,
RIGHT.
SO WE WANTED SOMETHING WITH
BETTER PHARMAICOLOGGIC
PROPERTIES, I'VE ALWAYS BEEN A
BIG PROPONENT OF SMALL MOLECULES
OR MAYBE TINY PEPTIDES BECAUSE
YOU HIT THE TARGET AND YOU RINSE
AWAY AND YOU GET NICE CLEAR
IMAGES.
SO WE STARTED WORKING ON THESE
UREAs AND I FOUND THEM BY
COINCIDENCE TALKING TO A CHEMIST
AT GEORGE TOWN WHO WAS WORKING
ON NALDACE INHIBITORS ARE AS CNS
PROTECT ANTS AND I SUGGESTED, I
HAVE A WAY BETTER IDEA, WELL
THE'S MOVE IT TO CANCER, SO, I
LOOKED AT HIS PORTFOLIO AND TOOK
THIS COMPOUND AND MADE A CARBON
11 LABELED VERSION FOR PET AND
WE SHOWED AND IN FACT I DID AN
INCREDIBLY THOROUGH STUDY WHERE
WE DID AN IN VIVO SKETCH OR
ANALYSIS.
WE WOULD DO THIS IN THE BRAIN
BUT I WAS STILL THINKING BRAIN
STUFF THEN.
SO WE DID IT IN THE PERIPHERY
AND WE SHOWED THAT THERE WAS--I
COULDN'T BELIEVE WE HAD ALL THIS
SPECIFIC BINDING TO ACTUALLY,
THESE WERE KIDNEYS, THESE WERE
RODENT KIDNEYS, BECAUSE I DIDN'T
REALLY HAVE A CANCER LAB, BUT
THERE'S A LOT OF PSMA IN THE
KIDNEYS AND WE SAW THAT--WE SAW
DECREASED SUBTAKE WITH A BLOCKER
SO THAT INDICATES SPECIFIC
BINDING, AND YOU KNOW EVEN IN
THAT PAPER, YOU KNOW WE
SUGGESTED THAT YOU KNOW WE CAN
MAKE IMAGING AGENTS, WE CAN MAKE
THERAPEUTIC AGENTS, THIS WILL BE
BE A GREAT BOOM TO CANCER
IMAGING AND THERAPY AND THEN A
FEW YEARS LATER I HAD--BY THEN I
HAD A LAB AND I HAD PEOPLE THAT
CAN MAKE XENOGRAPH ANDS WE
SHOWED THAT IT DID WORK IN
TUMORS.
AND THEN WE STARTED WORKING WITH
[INDISCERNIBLE] AND CO
CRYSTALLIZED SOME OF OUR
COMPOUNDS WITH THE RECOMBIN ANT
PROTEIN SO WE GOT A REALLY GOOD
SENSE OF JUST WHAT THE
STRUCTURAL REQUIREMENTS WERE FOR
THAT PARTICULAR TARGET.
BUT WE WERE STICKING WITH HALLOW
JEANS MAINLY, IT WAS A AN
ANOMALY, WE DID IT RIGHT OFF THE
BAT AND THEN WE STARTED MAKING
ALL THESE RADIO COMPOUNDS AND
FLOWERINNATED BACK IN 2003,
SOMETHING LIKE THAT I MET WITH
SHARING AG WHICH DOESN'T EXIST
ANYMORE BUT THEY TOLD ME THAT IF
THEY WERE GOING TO INVEST IN
SOMETHING LIKE THIS THAT HAD TO
BE FLOURIN 18, IN FACT, BEAR,
SIEMENS, THAT'S WHY I STUCK WITH
FLOURING, I THOUGHT THEY MUST BE
ON TO SOMETHING.
BUT IN THE UNITED STATES, FLOURK
R18 IS PART OF THE BUSINESS
MODEL, USING THESE ISOTOPES.
IT'S ALSO A BEAUTIFUL, THE
PERFECT PET ISOTOPE IN TERMS OF
ITS CHEMISTRY, IT'S--THE IMAGE
IT IS ARE NICE AND CRISP, IT HAS
A SHORT POSITRON PATH RAINCHL SO
WE MADE A BUNCH OF THESE RADIO
HALLOW GENERATEDDATED COMPOUNDS.
IN FACT THIS PYL IS THE 1 THAT
WE EVENTUALLY TOOK TO THE
CLINIC, THIS WAS A PRECLINICAL
PAPER IN 2011.
BUT THE OTHER THING WE TRIED TO
DO WAS LEVELS INCREASE RAMMING
THIS FOR THERAPEUTICS.
SO [INDISCERNIBLE] IS A
SYNTHETIC ORGANIC RADIO CHEMIST,
VERY TALENTED AND BY DOING VERY
BASIC DOCKING STUDIES WE SHOWED
THAT YOU NEED TO HAVE ABOUT
TWEBT INCAS TROMS BETWEEN THE
AFFINITY AGENT AND THE KEY LATER
TO GET PRODUCTIVE BINDING TO
PSMA, SO IN 08 WE HAD A COMPOUND
THAT WORKED AND WE PUT RENIUM IN
THERE AND WE SHOWED WE CAN DO
OPTICAL IMAGING, AND WE DIDN'T
DO THERAPEUTIC STUDIES AT THE
TIME BUT THAT IS THE--THIS IS
REALLY THE SCAFFOLD IS BASIS FOR
THE CURRENT THERAPY ANDA NUMBER
OF THETICS IN THE CLINIC BUT WE
DID MAKE A GALLIUM COMPOUND EVEN
THOUGH GALLIUM IS NOT QUITE AS
DESIRED OF AN ISOTOPE FOR A PET.
BUT IN THE UPPER LEFT CORNER WE
MADE A GALLIUM COMPOUND, BUT
THAT'S NOT THE 1 EVERYONE
ADOPTED, EVERYONE ADOPTED THE 1
ON THE RIGHT AND LEFT, WHICH HAS
THE HPDACCKEY-LATER AND THAT'S
BEEN APPROVED AND IS IN CLINICAL
USE.
OUR FIRST HUMAN STUDIES USING
THE INITIAL COMPOUND WHICH LOOKS
A LOT LIKE THE CARBON 11 XIPT WE
PUT A BENZO OUT THERE, BUT WE IT
WORKS WE SAW THE CANCER WITH
VERY HIGH SUVs BUT ALL THAT
OTHER ACTIVITY WAS UNDESIRABLE,
SO WE MADE AN ANALOGUE AND THE
ANALOGUE TOOK AWAY A LOT OF THAT
BINDING AND WE HAD A VERY NICE
COMPOUND WITH THIS PYL.
SO A FEW YEARS LATER, I GAVE A
TALK FOR THE PROSTATE CANCER
FOUNDATION.
AND I SHOWED THE AGENTS.
THIS SHOWS THE IMPORTANCE OF
ACADEMIC-TREY PARTNERSHIP.
SO THIS WAS ALL UROLOGIST ANDS
MEDICAL ONCOLOGISTS AT THIS
RETREAT.
IT WAS RIGHT HERE IN D. C. AND
YOU KNOW I SHOWED THESE NICE
IMAGES WHERE WE COULD--WE HAVE
SUVs OF LIKE A HUNDRED FOR
SOME OF THESE LESIONS AND
SOMEBODY JUST ASKED, YOU KNOW
WELL WHY CAN'T WE USE THIS THING
NOW?
AND I KNEW IN THE AUDIENCE WAS
THE CEO OF COMPANY WHO LICENSES
FROM US AND I SAID WELL, DON'T
CAN ME, ASK MARK BAKER WHY THIS
ISN'T--RIGHT?
AND I LITERALLY DID THAT AND
THERE ARE A FEW HUNDRED PEOPLE
AND THEY LOOKED AT HIM AND HE
COMMITTED TO DOING IT RIGHT
THERE ON THE SPOT.
SO THEN ONCE YOU HAVE THAT SORT
OF COMMITMENT, THEN YOU CAN
ACTUALLY MOVE THINGS BETTER TO
THE CLINIC.
SO HERE MEASURE LET ME SEE IF I
CAN, THERE IT IS, SO THE GOAL
WAS FOR THIS COMPOUND TO PICK UP
LESIONS THAT WERE IN SOFT
TISSUES LIKE IN THESE PERIAORTIC
LIMP NOS AS WELL AS IN BONE SO
WE WOULDN'T HAVE TO DO BONE
SCANS OR CT SCANS SO THAT WE CAN
HAVE A VERY NICE SPECIFIC
MECHANISM BASED TARGETED AGENT
FOR PROSTATE CANCER AND HERE
GERONTOLOGYSTSING BACK TO THE
ORIGINAL PARADIGM IN TERMS OF
HOW WE MANAGE PROSTATE CANCER,
THE IDEA WAS THAT WE COULD SEE
LESIONS NOW THAT ARE ACTUALLY IN
THE MARROW, THIS WOULD BE VERY
HARD, IMPOSSIBLE TO PICK UP
EITHER ON A BONE SCAN OR ON A CT
SCAN BUT YOU WILL SEE THAT WE'RE
IN THE SAME BALLPARK AS THE
CIRCULATING TUMOR DECKER NA SO
YOU MIGHT TAKE A PATIENT FROM A
HIGH RISK GROUP, DETECT THE
CANCER WITH THE INEXPENSIVE
BLOOD TESTS AND DO THE IMAGING
WHERE WE CAN SEE IT AND THEN YOU
CAN CALL YOUR FRIENDS LIKE
FUTRAN WHO'S A RADIATION
ONCOLOGIST AND HE CAN DO STEREO
TACTIC RADIATION AND HE CAN HIT
THAT LESION BEFORE YOU EACH KNOW
YOU'RE SICK.
SO AGAIN, EARLIER DETECTION AND
EARLIER TREATMENT AND YOU CAN
STERILIZE THAT PART OF THE BODY
IN TERMS OF THE CANCER AND YOU
CAN CURE THERE'S VARIOUS
CLINICAL SPACES THAT I WILL NOT
BELABOR PRESURGICAL STAGING AND
HIGH RISK PATIENTS, BIOCHEMICAL
OCCURRENCE ISSUES THESE ARE 2
THE 2 MAIN THINGS FOR THERAPY,
MONITORING, SELECTING FOR THE
THERANOISTICS BUT I WILL ONLY
SHOW 1 MORE NUANCED THING THAT
WE CAN DO WITH AGENTS LIKE THIS.
SO THERE'S SOMEBODY AT HOPKINS
NAMED SAM [INDISCERNIBLE].
HE'S A MEDICAL ONCOLOGIST WHO
FOCUSES ON PROSTATE CANCER AND
HE HAS THIS IDEA OF SORT OF
FREAKING OUT THE CANCER THROUGH
THIS BIPOLAR ANDROGEN THERAPY.
SO PROSTATE CANCER NEEDS
ANDROGENS TO SURVIVE.
IN FACT, EVEN IN PATIENTS THAT
ARE CASTRATED, THE ANTIGEN WILL
FIGURE OUT HOW TO GET THEM.
BUT HE SAYS, OKAY, I WILL TAKE
PASHT AND I WILL GIVE A PATIENT
WHO'S CASTRATE, AND I WILL GIVE
HYMN A TON OF TESTOSTERONE AND
THEN WHAT'S THE TUMOR GOING TO
DO WITH THAT, AND THEN THE TUMOR
GOES INTO APOPTOSIS BECAUSE IT'S
ALL OF A SUDDEN IT'S ENRICHED
WITH WHAT IT'S ALWAYS WANTED SO
IT KIND OF ODs ON THAT AND
THIS WAS HIS IDEA FOR THERAPY
AND ACTIVITIES AND PROJECTS
COMPETENT IT WORKS SOMETIMES,
BUT WHAT WE CAN DO TO TRY TO
INCORPORATE THAT INTO THIS
THERAPY SO HERE WE HAVE 6
PATIENTS AND THEY GET A BASE
LINE PSN8 PET KAN--KANA AND
FOLLOW UP SCAN FOLLOW UP 3
MONTHS LATER AND SOME PATIENTS
LIKE PATIENTS 1-3 THEY GET
BETTER SO LIKE FOR EXAMPLE,
HERE'S A LESION, IT'S GONE, THAT
PATIENT DID BETTER, HERE'S
LESIONS HERE, THEY'RE GONE,
THESE PATIENTS HOWEVER, 4-6,
THEY TENDED TO GET WORSE, SO, IT
WORKS ON YOU KNOW SOME PATIENTS
BUT NOT EVERYBODY.
SO WHAT'S INTERESTING IF YOU DO
CONVENTIONAL IMAGING AT THE SAME
YOU DO THE SMA PET SCAN,
EVERYBODY LOOKS GOOD EMPLOY SO
WE HAVE 1 PATIENT WITH RESPONSE,
EVERYBODY ELSE WITH STABLE
DISEASE INCLUDING THOSE THAT
PROGRESSED BUT AUTOLEASTOT PSMA
SCAN WE KNEW 3 MONTHS EARLIER
WHO WAS PROGRESS, SO WE COULD
PREDETECTED WHO'S GOING TO
PROGRESS USING THE MOLECULAR
IMAGING AGENT AS OPPOSE TO JUST
CONVENTIONAL IMAGING, SO BUYING
THAT TIME AND GETTING THAT
EARLIER DIAGNOSE REALLY ENABLES
YOU TO MAKE GOOD DECISIONS, SO
WE'VE DONE ALL SORTS OF STUFF
WITH THESE PSMA MOLECULES, WE
HAVE AN OPTICAL AGENT THAT WAS
LICENSED BI A COMMERCIAL CONCERN
THAT IS USED FOR SURGICAL
GUIDANCE AND THERE'S A CLINICAL
TRIAL CAN WE'VE MADE PHOTO
ACOUSTIC IMAGING AGENTS, DUAL
MODALITY AGENTS, SO THAT WE CAN
USE THE OPTICAL OR WE CAN USE
THE RADIO NUCLEOTIDES BASE PART
OF IT TO MAKE THE DIAGNOSIS
AND/OR DETECT THE CANCER AND
THEN THE NEXT DAY IN THE O. R.
WE CAN SEE IT AND MAKE SURE
THERE'S A NEGATIVE SIRNLGICAL
MARGIN.
WE CAN DETECT IT USING
SATURATION TRANSFER OR MR
IMAGING SO WE THOUGHT OF A
NUMBER OF USES FOR THIS, 1 OF
THOSE IS THE THERAPY, SO WE GOT
A LITTLE BIT DEEPER INTO THE
THERAPY, MY INTRODUCTION TO
RADIO FORM SUITICAL THERAPY GOES
WAY BACK AND I LITERALLY I READ
THIS PAPER ALSO IN REALTIME.
THIS PAPER WAS GIVEN TO ME BY MY
RESEARCH ADVISOR IN THE FALL OF
1982 AND ONCE AGAIN, WHERE'S THE
WORK BEING DONE, RIGHT HERE AT
THE NIH.
BUT THEY TOOK CELLS, BREAST
CANCER CELLS AND FROZE THEM DOWN
WITH [INDISCERNIBLE]
IODESTRADISCIPLINARYOLE, THAT
THAT YOU COULD KILL BREAST CANC
THEY'RE WAY SO THE POINT BEHIND
THIS IS WE HAVE BEEN THINKING
ABOUT THIS STUFF FOR A LONG
TIME, OKAY, THIS IS ALREADY, AND
I'M NOT TALKING ABOUT RADIO
IODINE, I'M TALKING ABOUT USING
CHEMIST RADIOY TO GENERATE
COMPOUNDS THAT DIDN'T EXIST TO
TREAT CANCER, YOU KNOW OVER 40
YEARS AGO.
I PERSONALLY HAVE BEEN IN THIS
FOR OVER 40 YEARS, SO WHAT
MAYBES IT DIFFERENT NOW IS THAT
NOW WE ACTUALLY HAVE BUY-IN FROM
THE MEDICAL COMMUNITY AND FROM
INDUSTRY, PARTICULARLY NOVARTIS,
IF IT WASN'T FOR NOVARTIS, THIS
WOULD BE MAINLY IN ACADEMIA.
BUT I'VE LEARNED SOME HARD
LESSONS ALONG THE WAY.
SO WE MADE A COMPOUND, 1 OF OUR
PSMA COMPOUNDS, THIS IS I THINK
THIS IS THE GALLIUM, GALLIUM 68
VERSION AND I CALLED RICHARD
BAUM 1 OF MY FRIENDS IN GERMANY,
I DID THIS WITH AN IMAGING AGENT
BECAUSE I KNEW IT WOULD BE SAFE
AND I DIDN'T HAVE TO WORRY ABOUT
ANY TOXICITY, BUT RICHARD IN
EUROPE, YOU CAN TBIF THINGS TO
PATIENTS WITHOUT
NECESSARILY--IT'S A
DOCTOR-PATIENT RELATIONSHIP
BASICALLY THAT ENABLES YOU TO
GIVE THINGS THAT AREN'T
NECESSARILY APRUFFED BY THE FDA
SO I WAS DYING TO KNOW HOW THIS
COMPOUND WORKED AND I GAVE A
LITTLE BIT TO RICHARD AND HE
GAVE IT TO 1 OF HIS PATIENTS AND
WE HAD BEAUTIFUL IMAGES WITH
THIS COMPOUND.
JUST REALLY GORGEOUS IMAGES SO I
SAID WOW, LET'S PUT LUTECIUM IN
THERE AND SEE IF WE CAN CURE THE
PATIENT SO WE DID THE LUTICIUM,
AND IT DEPARTMENT WORK THAT
IMRAIT.
WE MADE 1 WITH PROVICTO, YOU CAN
SEE IT, WE DON'T SEE MUCH WITH
OUR COMPOUND SO THEN I LEARNED
THAT BY CHANGING OUT THE METAL
AND THE SUBTLE CHANGES YOU HAVE
TO THE KEY LATER, ET CETERA, CAN
YOU TOTALLY 3 OFF YOUR
PHARMACOKINETICS AND NOT HAVE A
GOOD [INDISCERNIBLE] ANYMORE.
SO WE TALK ABOUT THIS AS AN
THERAPY BUT THERE'S MORE TO IT
THAN THAT.
I REMEMBERED THAT PAPER FROM
LIPPMAN, AND I TRIED LET'S TRY
AN ELECTRON EMITTER, FOR THESE
YOU NEED TO BE RIGHT UP AGAINST
THE DNA AND I KNEW FROM OUR
FLUORESCENT COMPOUNDS THAT THE
PSMA WHICH IS THE CELL SURFACE
PROTEIN WOULD BE INTERNALIZED
AND WOULD GET RIGHT UP INTO THE
SENT RHIZOME INTO THE NUCLEUS SO
I THOUGHT IT WOULD WORK IF I PUT
I125, AND I125 IS CHEAP AND EASY
TO GET AND SYNTHESIZED WITH, SO
WE TRIED THAT AND WE HAD ANIMALS
THAT EITHER EXPRESSED PSMA, DOWN
HERE AND THEN OTHER ANIMALS DID
NOT.
SO THIS IS A METASTAT BEING
HUMAN PROSTATE CANCER.
IF YOU EXPRESS THE TARGET, YOU
DON'T DEVELOP THE CANCER BECAUSE
YOU COMBINE TO OUR OJ ELECTRON
EMITTING COMPOUND.
SO I THINK THAT OJ ELECTRONS ARE
SOMETHING WE SHOULD THINK MORE
ABOUT.
THIS IS SOMETHING I GOT FROM
JONATHAN SIMONS, IT HAS BEEN
PUBLISHED, AND THIS NOW MICHAEL
HANDOFF MAN'S WORK IN AUSTRALIA
BUT IT SHOWS HOW YOU CAN TAKE
PATIENTS WITH A PSA OF A
THOUSAND AND YOU CAN TAKE OUT
ALL THEIR TUMOR AND THEY CAN
HAVE A VERY IMPROVED QUALITY OF
LIFE.
AND IF YOU USE AN EVEN STRONGER
COMPOUND, LIKE AN ALPHA PARTICLE
EMITTER LIKE 225, EVEN AFTER
FAILING THE LUTISSUING ICIUM
THERAPY AND ACTIVITIES AND
PROJECTS COMPETENT HAD IS NOT
OUR WORK, BUT YOU CAN ACTUALLY
STILL IMET RID OF ALL THE TUMOR,
THE TROUBLE HERE IS THAT YOU GT
RID OF THE SALIVARY GRANDS, THIS
IS NOT A STUDY WE COULD HAVE
DONE IN THE UNITED STATES BUT
THIS PEASHT WILL HAVE TO USE A
SQUIRT BOTTLE THE REST OF THEIR
LIFE UNFOR THEINATELY BECAUSE OF
THE--UNFORTUNATELY BECAUSE OF
DOING THAT.
SO WE DEVELOPED OTHER COMPOUNDS
THAT ARE AT LEAST IN ANIMAL
MODELS THEY LOOK JUST AS GOOD AS
THE PROVICTO, BUT THEY DON'T
BIND TO THE SALIVARY FLANKEDS
AND WE LEARN THAT THANKS TO PETE
TROYKE.
AND WOB OF THE GREAT THINGS AT
THE NIH, IF YOU CAN FIND
SOMEBODY TO WORK WITH IN THERE
LIKE PETE, HE SAID YEAH, LET'S
SCAN SOME PATIENTS WITH YOUR NEW
THING, I SAID WHAT, YOU CAN JUST
SCAN.
HE SAID YEAH, WE'LL DO A HUNDRED
PATIENTS OR SO.
WHICH IS UNIMAGINABLE FOR ME
EMPLOY SO FORTUNATELY PETE DID
THAT AND SHOWED THAT WE DON'T
GET SALIVARY DPLAND UPTAKE WITH
THESE COMPOUNDS BUT WE STILL CAN
SEE ACTIVITY IN THE CANCER, NOT
NICE AND CRISP AS WELL AS THE
617, BUT THIS A VERY IMPORTANT
DETAIL THAT WE DON'T GET, HIT
SALIVARY FLANKEDS AND WE DON'T
HIT THE KIDNEYS AS MUCH SO THIS
COMPOUND, THE ACTINIUM LABELED
VERSION IS JUST BEGINNING NOW.
A CLINICAL TRIAL SPONSORED BY
NOVARTIS.
AND YOU KNOW AGAIN, ALPHAS ARE
GOING TO BE THE WAY TO GO, BUT
WE DID A THERE WAS A LUTICIUM
TRIAL, WAS DONE MANICALLY TO GET
THE DOSEEMETRY FOR THIS TRIAL.
THIS IS JUST BEGINNING AND I
HOPE THAT YOU AND OTHER SITES
WILL BE INTERESTED.
BUT I THINK THAT ACTINIUM IS
OVERKILL.
I THINK IT'S DAUGHTER ALPHA
PARTICLES THAT COME OFF, 4 ALPHA
CERTAINLY--CERTAINLY MISSIONS
AND AFTER THE FIRST EMISSION YOU
GET A RECOIL EEIVET SO YOU LOSE
TRACK OF YOUR RECEPTOR AND THEN
ALL THE OTHER ALPHAS GO WHEREVER
THEY WANT, SO IT'S NOT REALLY
THAT GREAT IN TERMS OF TOXICITY
SO I'VE BEEN WORKING WITH
MICHAEL ZALUTSKY AND WE'VE BEEN
WORKING WITH A VERSION OF OUR
COMPOUNDS IT'S A TAMER KINDER
GENTLER PARTICLE BECAUSE IT'S
GOT 1 DECAY AND WE'RE HOPE THOG
BRING THAT TO THE CLINIC PRETTY
SOON BUT JUST AS A CAUTIONARY
TAIL TO MYSELF, WE ALSO
SYNTHESIZED A DRUG LIKE
COMPOUND.
SO ANTIBODY DRUG CONJUGATES
OFTEN USE HORRIBLE CYTOTOXIN
KNOWN AS MONOMETHYL ORASTATIN.
VERY TOXIC AND YOU NEED TO BRING
AN ANTIBODY TO BRENG IT TO THE
CANCER BUT STILL IT'S KIND OF
TOXIC BUT WE MADE A COMPOUND
THAT HAD 2 LEVELS INCREASES OF
SECURITY WHERE WE HAD SPECIFIC
CANCER TARGETING FROM THE
[INDISCERNIBLE] AND THEN WE PUT
A CLEAVABLE LINKER THERE SO THAT
ONCE THIS IS CLEAVED YOU
ACTIVATE THE TOXIN AND WE FINE
THAT THIS MOLECULE IS JUST AS
GOOD, AS ANY OF OUR RADIO
THERAPEUTICS.
SO, YOU KNOW THE RADIO
THERAPEUTICS ARE GREAT, THEY
PROBABLY HAVE LESS SIDE EFFECTS
BUT IF YOU DESIGN A DRUG
CAREFULLY YOU COULD PROBABLY
ALSO HAVE--THIS IS BEASKLY A
NONTOXIC DRUG AS WELL, SO JUST
PIVOT FOR 1-SECOND AWAY FROM THE
PSMA.
THERE'S ANOTHER TARGET YOU HEARD
ABOUT, SO HAD IS A TYPICAL
PICTURE THAT YOU MIGHT HAVE SEEN
IN MED SCHOOL IF YOU WENT TO MED
SCHOOL WHEN PETE AND I DID IN
THE EARLY 1980S.
AND YOU KNOW STROMA WHICH WE'VE
ALL KIND OF--WE WOULD BLOW IT
OFF, BUT IT TURNS OUT THAT
STROMA IS THE MOST IMPORTANT
THING NOW.
IT'S MAISHZING HOW THAT HAPPENS
IN MEDICINE, HA'S WHERE THE
FIBROBLAFS ARE, THE MACROPHAGES
ARE AND WE'RE SPENNING A LOT OF
TIME TRYING TO IMAGE THESE AND
WE ACTUALLY USE THIS 2 C
YANO-[INDISCERNIBLE], THE BEST
POST DOCKER NEXT TO DEEMA, BUT
XING YANG UNBELIEVABLE FOWBD
THIS AND STARTED
FUNCTIONALLIZING IT FOR
FIBROBLAST ACTIVATION PROTEIN
AND WE GET NICE HIGH PERCENT ID
PERGRAM EMPLOY WHICH IS WHAT YOU
WANT ON SEE, WE ALSO FIND THAT
THE SPECIFIC ACTIVITY IS VERY
IMPORTANT THAT IF WE HAVE HIGH
SPECIFIC ACTIVITY WE ACTUALLY
HAVE MORE UPTAKE IN THE BLOOD.
SO WE NEED TO HAVE A LINGS
BIT--IME SORRY, THIS IS THE,
WE'RE GETTING CARRIER IN THIS
CASE, SO WE HAVE HIGHER UPTAKE
IN THE BLOOD WHEN WE DON'T HAVE
CARRIER.
SO THERE'S ALL SORTS OF
CONSIDERATIONS WE TAKE BO EFFECT
FOR IMAGING AND FOR THERAPY.
THE OTHER THING IS, THAT WITH
ENZOLIEWTA MID, AND AGENTS LIKE
PROVECTO, YOU EVENTUALLY GET RID
OF ALL YOUR CANCER AND ALL
YOU'VE GOT LEFT IS CANCER THAT
YOU CAN'T SEE.
SO IT'S EITHER NEUROENDOCRINE
DEDEFERENTIATED OR SOME OTHER
PHENOTYPE EMPLOY SO WE DEVELOPED
A COMPOUND THAT WOULD BIND BOTH
FAP, WHICH HAS BEEN SHOWN TO BE
TAKEN UP IN NEUROENDOCRINE
PROSTATE CANCER AS WELL AS PSMA,
SO THAT WOE CAN HIT, GET JUST
ABOUT ALL THE CANCER WE CAN
THINK OF BUT I CAN TELL YOU 1
THING FOR SURE THAT THE CANCER
WILL FIGURE OUT ANOTHER WAY,
EVEN THESE MOLECULAR RADIO
THERAPEUTICS, WE USED TO SAY YOU
CAN'T MUTATE AWAY FROM THESE
THINGS BUT OKAY, WELL, IF YOU
DON'T DO THAT, THEN YOU JUST
SELECT FOR THE 1 OR 2 CLONES
THAT DON'T EXPRESS THE TARGET.
AND WE WANT TO TRY TO GET AROUND
THAT ALSO.
OOPS.
LET'S SEE IF THIS--THERE WE GO,
SO IN TERMS OF DRUGS TO TREAT
PROSTATE CANCER, WE HEAR A LOT
ABOUT THESE RADIO THERAPEUTICS,
HERE'S THE--I GUESS IT'S THIS
KIND OF PINK HERE, IT DOESN'T
LOOK TOO ENCOURAGING IN TERMS OF
WHAT'S GOING TO BE USED IN THE
FUTURE.
NOW THIS PAPER'S ALREADY A
COUPLE YEARS OLD BUT YOU KNOW
FROM WHAT I HEAR FROM PATIENTS
THEY LOVE THIS STUFF.
IT'S FLYING OFF THE SHELVES, AND
THAT'S BECAUSE THE SIDE EFFECT
PROFILE IS SO MUCH BETTER THAN
WHAT THEY'RE USED TO WITH CHEMO
THERAPY, BUT IN THE FUTURE, YOU
KNOW THERE MIGHT BE P A RP
INHIBITORS IN CERTAIN
SUBPOPULATIONS, AGAIN A
PRECISION TECHNIQUE, BUT WE'LL
SEE, YOU KNOW WHERE THESE ARE
GOING TO SHOW UP IN THE FUTURE,
BUT THE MOST IMPORTANT TARGET
REMAINS THE ANTIGEN RECEPTOR
DIRECTED THERAPIES EVEN THOUGH
THEY DON'T REALLY PROVIDE LONG
LASTING RESULTS.
BUT THEN WHAT DOES?
AND I'LL TALK ABOUT THAT IN A
MINUTE.
SO THE LAST COUPLE MINUTES I
JUST WANT TO SAY THAT, YOU KNOW
WE'RE BEGINNING TO APPLY MACHINE
LEARNING TO A CERTAIN EXTENT,
TRYING TO TRAIN THE MACHINES
WITH SOME OF OUR NEW AGENTS SO
WE CAN MAKE VERY SPECIFIC
RECOMMENDATIONS TO PATES, FIGURE
OUT SORT OF IN A PRECISION WAY
WHO'S 2 FRAIL TO UNDERGO THE
THERAPY, WHAT KIND OF DOSING
THEY SHOULD HAVE, BUT BEFORE WE
GO CRAZY WITH MACHINE LEARNING,
I'D LIKE TO SHOW THIS SLIDE
WHERE WE CAN TRAIN A
CONVOLUTIONAL NETWORK ON A
MILLION BONE SCANS AND THAT
CNN WILL BE ABLE TO DETECT
CANCER CERTAINLY BETTER THAN I
CAN, PROBABLY NOT BETTER THAN
YOUR NUCLEAR PHYSICIANS MEDICINE
HERE BUT VERY SMART.
THE CNN CAN WILL IT THE
DIFFERENCE BETWEEN A RIB
FRACTURE AND A METASTASIS, BUT
IN THIS CASE, OUR FRIEND FROM
RADIATION ONCOLOGY SAID SHOULD
WE RADIATE THIS LESIONION, THIS
METASTATIC FOCUS AND WE
RECOMMENDED DOING A PSMA PET
SCAN AND YOU COULD SEE THAT
WOULD NOT HAVE NOT BEEN--IT
WOULD HAVE BEEN FUTILE.
SO WE'RE STILL AHEAD OF THE
MACHINES SO WE STILL NEED
DISCOVERY, SO THAT WE CAN
DISCOVER NEW AGENTS LIKE THIS
AND THEN WEB CONNECTED TRAIN THE
MACHINES ON THESE AGENTS WHICH
IS WHAT'S HAPPENING NOW BUT
WE'RE ARK HEAD OF THE MACHINES
BUT NOT BY MUCH, I HAVE TO SAY,
AND THE GAP IS CLOSING BUT WE
STILL NEED TO UNDERSTAND THE
CHEMIST RADIOY AND THE TARGETS.
--CHEMISTRY AND THE TARGETS.
STEVE ROW AND OUR GROUP HAS
DEVELOPED A STRUCTURED REPORTING
SYSTEM AND NOW WOE HAVE WAYS OF
AUTOMATICALLY DETECTING AND
SEGMENTING THESE LESIONS SO THAT
FOR EXAMPLE, WE CAN JUST LET THE
ALGORITHM FIND THESE LESION ANDS
WE CAN GO TO INNER HARBOR, GET
SOME SOFT SHELL CRABS, COME BACK
AN HOUR OR 2 LATER AND MAKE SURE
THE MACHINE WAS CORRECT.
SO WHAT WE TRY TO DO NEXT IS
DETECT AND LOCALIZE THEM
AUTOMATICALLY, DISSECT THEM
AUTOMATICALLY, EXTRACT FEATURES.
WHAT WE HAVEN'T DONE YET BECAUSE
IT'S TAKEN US 2 YEARS TO GET
PAST THE IRB BUT WE CAN USE
MEDICAL HISTORY ALSO AND THEN WE
CAN MAKE REALLY INFORMED
TREATMENT TECISIONS LIKE WE CAN
BE REALLY SPECIFIC WITH THE
PATIENTS THAT WE'RE SEEING,
WHICH IS SORT OF THE FUTURE, WE
HAVEN'T DONE THIS YET, BUT THIS
IS ALL AUTOMATED AND MERELY
CURATED BY THE RADIOLOGIST.
I PERSONALLY BELIEVE THAT BY
KOAM BIENING THE
POWER--COMBINING THE POWER OF
ARTIFICIAL INTELLIGENCE AND THE
SPECIFICITY AND THE SENSITIVITY
WITH MOLECULAR IMAGING THAT WE
CAN PROBABLY GET AS CLOSE TO
HUMAN BIOCHEMISTRY ENVIVO AS YOU
CAN POSSIBLY GET IN 2023.
BUT STILL THERE'S SO MUCH FOR US
TO DO.
A LOT OF DOORS HAVE OPENED,
MAINLY THROUGH CLOUD COMPUTING,
THROUGH DISCOVERY OF NEW
TARGETS, IN THE OLD DAYS I WOULD
READ ARTICLES LIKE I SHOWED YOU
AT THE BEGENERATEDDING IN JMED
CAM AND I WILL FIND, THAT LOOKS
LIKE A GOOD TARGET BUT NOW
THERE'S SO MANY TARGETS, IT'S
LIKE I DON'T KNOW WHERE TO
START, I MEAN IF I--1 TRICK CAN
YOU USE, YOU LOOK AT, WELL WHAT
ARE THEY MAKING ANTIBODY DRUG
CONJUGATES TOWARD, SO I LOOK AT
THAT.
AND EVEN THAT YOU COULD
DOWNLOAD, YOU KNOW JUST
SPREADSHEETS WITH 400 TARGETS
LIKE WHERE DO YOU PUT YOUR
NICKEL DOWN, SO WOE GOT LUCKY,
FRANKLY WITH THIS PSMA.
BUT STILL, THERE'S SO MUCH TO
DO, THIS WAS THE REGISTRATION
TRIAL FOR THE 617, NOW KNOWN AS
PLUVICTO EMPLOY YOU CAN SEE THEY
ADDED THE PLUVICTO TO THE
STANDARD OF CARE AND THEY GOT A
BUMP PRACTICES 11 MONTHS TO 15
MONTHS.
I WAS PERSONALLY DISAPPOINTED.
I THINK A LOT OF PEOPLE,
PARTICULARLY AT NOVARTIS, THEY
WERE THRILLED BUT I'M THINKING
THAT'S A PRETTY WIMPY RESULT.
ESPECIALLY IF YOU TAKE PATES AT
A THOUSAND AND IT MOVINGS TO 0,
HOW ARE THESE CURVES SO CLOSE?
IT'S RIDICULOUS.
BUT IT'S BECAUSE THERE'S CANCER
THERE, WE SELECT FOR THE CANCER
THAT YOU CAN'T SEE ANYMORE.
SO THAT WAS THE RESULT, SO BOTH
KAPLANMIER KERVES TOO CLOSE FOR
COMFORT.
THIS JUST CAME OUT YESTERDAY.
ANOTHER RESULT WHICH SOUNDS
IMRAIT ON PAPER, THEY HAD
A--THEY MET THEIR PRIMARY END
POINT AGAIN WITH THE PLUVICTO.
THEY SHOWED THAT YOU KNOW THE
PRIMARY END POINT IN THIS CASE
WAS RADIO IMROFFIC PROGRESSION
FREE SURVERIFIAL WHICH WAS MET
AND THERE WAS, TREMENDOUSLY NICE
RESULT TO SEE, YOU KNOW 60% OF
PATIENTS I THINK HAD EXCELLENT
PSA RESPONSES, ET CETERA.
AND IT DID BETTER THAN THE
THERAPY THAT THEY WERE COMPARING
IT TO, THEY WERE COMPARING IT TO
A CHANGE FROM [INDISCERNIBLE],
WHICH FRANKLY IS A STRAW MAN TO
PUT YOUR DRUG UPAGAINST, BECAUSE
IF YOU FAIL 1, YOU'RE PROBABLY
NOT GOING TO DO THAT GREAT WITH
THE OTHER, IT'S SORT OF LIKE
ANOTHER KIND OF--KIND OF A WIMPY
TRIAL.
I SHOULDN'T SAY THAT NOW, I'VE
SAID IT ALL OVER THE INTERNET,
BUT I'M NOT THE ONLY 1 WHO'S A
LITTLE BIT SKEPTICAL, IT'S OVER
ALL VERY POSITIVE, YOU KNOW THEY
DID, THEY DID DECREASE THE OR
THEY INCREASED PROGRESS FREE
SURVIVAL AND THE KAPLAN MIER
KERVES ARE FURTHER APART,
INSTEAD OF LIKE THIS, THEY'RE
LIKE THIS.
BUT AS FAR AS I'M CONCERNED
UNTIL THEY'RE LIKE THAT, YOU
KNOW I'M JUST NOT GOING TO BE
LIKE MEGAIMPRESSED, OKAY.
SO THIS IS WHAT WE WANT.
WE WANT THE LINE TO GO ALL THE
WAY ACROSS.
THAT'S WHAT RATS LIKE FOR THE
CHECK POINT INHIBITORS, SO
UNFORT MATILY FOR THE CHECK
POINT INHIBITORS ONLY LIKE THAT
FOR MAYBE 20% OF THE PATIENTS.
THAT'S THE PROBLEM.
SO I ACTUALLY SAW JIM ALLYSON
GAVE A VERY NICE TALK WHERE THEY
HAVE THOSE CURVES WHERE MAY IMET
A DURABLE RESPONSE APPROXIMATE
HE SAID THAT OKAY, WE ONLY GET
IT IN 20% OF THE PATIENTS SO YOU
GIVE ME 5 CHECK POINT
INHIBITORS, THATIA A HUNDRED%,
RIGHT?
BUT, YEAH, UNFORTUNATELY,
TOXIC--TOXICITY DOESN'T WORK
LIKE THAT, BUT THIS IS THE GOAL.
THIS IS STILL A NICE STEP IN THE
RIGHT DIRECTION OKAY WITH THIS
PUNISHING SMA 4 TRIAL, IT'S IT
NEEDS A LITTLE BIT MORE, I
COMPOUND NEEDS MORE VALIDATION
AND MORE CHALLENGING CLINICAL
TRIALS LIKE AGAINST CHEMO
THERAPY BUT ANYWAY, SO THE WAY I
LOOK AT WHERE RADIOLOGY'S GOING
IS THAT SCIENCE ISSUES MEDICINE
AND IMAGING ARE GOING TOWARD
HIGH VALUE PRECISION CARE
AUGMENTED BY RAPIDLY EVOLVING
MACHINE LEARNING TECHNOLOGY AND
I WOULD REALLY LIFE TO SEE
PHYSICIANS MORE ENMESHED IN THIS
PROCESS BECAUSE IT'S
REALLY--IT'S OUR FIELD.
AND WHEN I SAY INNOVATION, I
WANT TO BE SPECIFIC ABOUT
INNOVATION, SO PEOPLE THROW THAT
WORD AROUND A LOT BUT THIS I GOT
FROM A GUY NAMED ASK WE'RE
TALKING ABOUT INNOVATION AND THE
IDEA IS THAT THE CURRENT CULTURE
IN ACADEMIC MEDICINE IS TO HAVE
AN IDEA, TEST AS HYPOTHESIS, YOU
WRITE A PAPER, YOU WRITE A
GRANT, ET CETERA THAT'S THE
TRADITIONAL WAY OF DOING THINGS
BUT WHAT WE NEED TO DO AND
WHAT'S HAPPENING MORE
PARTICULARLY BECAUSE OF TECH
TRANSFER OFFICES AND WHAT NOT,
WE'RE MOVING FROM THIS SORT OF
CURRENT CULTURE, THIS LEARNING
MODEL, TO MORE OF AN INNOVATING
MODEL WHERE WE WORK BACKWARDS
FROM UNMET NEEDS, OKAY, WHERE WE
DEVELOP NEW WORK PROD
UBIQUITINNATIONS LIKE I CONSIDER
THE PYL IS SOMETHING THAT YOU
KNOW THERE WAS AN UNMET NEED AND
THAT WAS PROSTATE CANCER, YOU
COULDN'T REALLY DETECT IT WELL
WITH IMAGING, FDG DIDN'T WORK,
THEY DIDN'T HAVE A LOT OF MRI AT
THAT TIME, IT WAS AROUND
BUT--SO, WORKING BACKWARDS FROM
AN UPMET NEED, THAT'S AN
ENGINEERING APPROACH, THAT'S
WHAT AI DOES, YOU DON'T REALLY
KNOW HOW AI GETS TO ITS
SOLUTIONS BUT IT DOES.
SOMETIMES IT TAKES YOU WAY OFF
BASE BUT IN ANY EVENT THAT'S THE
INMODEL CITIZENIVATING MODEL
THAT I THINK WE WILL BE SEEING
MORE BECAUSE THAT'S WHERE THE
TRANSFORMATION OCCURS, SO WHEN
YOU HAVE FOR EXAMPLE, AMAZON
RIGHT, STARTED OUT AS A BOOK
STORE, NOW NOBODY GOES TO
SHOPPING MAULS, THAT'S
INNOVATION, THAT'S REALLY
TRANSFORMATION SO WHAT WE NEED
TO HAVE HAPPEN IS WE NEED TO
HAVE PHYSICIANS, GENERATION Z
PHYSICIANS THAT ARE BORN INTO
USING IPHONES, LIKE I HAVE A 6
YEAR-OLD DAUGHTER AND SHE KNOWS
HOW TO SKOAL AND THERE'S PEP
A PIG AND SHE WILL HIT THAT AND
JUST DIGITAL NATIVES, THEY
SHOULD WORK HAND AND GLOVE WITH
THE PROFESSIONAL SCIENTISTS HAVE
YOU HERE AND REALLY KIND OF MOVE
THINGS OUT INTO THE CLINIC MORE
QUICKLY THAN THEY CAN BE.
SO WITH THAT I WANT TO THANK OUR
COALITION OF MOLECULAR IMAGING
EXPERTS, THESE ARE ALL FACULTY
IN THIS COALITION WITH THESE
STUDENTS AND THANK YOU FOR YOUR
ATTENTION.
THANKS.
[ APPLAUSE ]
HAPPY TO ANSWER QUESTIONS IF
THERE ARE ANY OR TIME.
I GUESS I WENT OVER.
>> THAT WAS AN EXCELLENT TALK
AND 1 OF THE THINGS--I HAVE 2
QUESTIONS, 1 IS WE'RE TALKING
ABOUT HOW LET'S SAY UNIMPRESSIVE
OR NOT AS DPOA AS WE WOULD HAVE
LIKED THE OUTCOMES TO BE WITH
RESPECT TO PFS AND OS WITH THE
PSMA PHARMACEUTICAL THERAPY CAN
YOU COMMENT ON PERSONALIZED
DOSEMTREE AS WAY TOY OPTIMIZE
THAT BET XER THEN THE OTHER
QUESTION I HAVE SOMEWHAT RELATED
IS, YOU KNOW DO YOU THINK WE CAN
SYSTEMATIZE TARGET
IDENTIFICATION THAT WE CAN
DEVELOP PROBES AGAINST AND
ULTIMATELY GO TOWARD RADIO
PHARMACEUTICALS OR ARE WE
RELEGATED TO THE SPREADSHEETS
YOU REFER TO.
THOSE ARE GREAT, VERY GOOD
QUESTIONS, SO FOR THE DOSE
EMTREE IS GOING TO HELP, SO FOR
EXAMPLE, THE PRUVICTO AND ALL
THE TRIALS WORE GOING TO DO
BASED ON SOME ARTIFICIAL NUMBER
23 GRAY TO THE KIDNEY WAS
SOMETHING THAT WAS DEVELOPED FOR
EXTERNAL BEAM RADIATION YEARS
AGO THAT HASN'T REALLY BEEN
TESTED AND I THINK THAT WE MAYBE
UNDERDOING A LOT OF THESE
PEASHTS.
BUT THERE'S EVERY INDICATION
THAT WE'RE NOT BECAUSE NOT
EVERYBODY IS ABLE TO TOLERATE
ALL 6 CYCLES OF THE THERAPY.
SO IF EVERYBODY WHIZZED THROUGH
THE SICK CYCLES THEN YOU WOULD
THINK THAT YOU KNOW MAYBE WE ARE
UNDERDOING BUT AT SAT SAME TIME,
THESE PATIENTS ARE EXTREMELY ILL
AND AND NOW AS WE MOVE THIS UP
FURTHER, PSMA 4 THOSE ARE
PATIENTS THAT HAD NOT HAD THE
SAME THERAPY EMPLOY I THINK WE
WILL SEE THAT WE WILL GET BETTER
RESULTS AND I THINK THE
DOSEMTREE WILL HELP IF WE CAN
HELP TO AN MTD WE HAVEN'T HAD
EXCEPT A DOSE MITT RICK MTD AND
I THINK THOSE ARE COMING.
AND THE SECOND PART ABOUT
SYSTEMATIZING THE TARGETS IS
THAT WE CAN USE AI AND WE HAVE
AN UNDERGRAD IN OUR GROUP NOW
WHO IS--DOESN'T KNOW ANYTHING
ABOUT CHEMISTRY SO I PUT HIM TO
THE TEST, HE'S A BIOMEDICAL
ENGINEER AND I SAID HERE'S SOME
COMPOUNDS, I WANT YOU TO MAKE A
NEW DRUG FOR US ACROSS THE BLOOD
BRAIN BARRIER AND HE DID, HE HAD
IN GOOD CANDIDATES.
NOW WE HAVE TO GO MAKE THEM BUT
IT'S LIKE HE DID THAT
WITHOUT--BY BEING ABLE TO
SYSTEMATICALLY PUT THESE DRUGS
INTO SMILES CONSTRUCTS AND THEN
RUNNING THEM THROUGH HIS
PROGRAMS AND SO I THINK THAT
THAT KIND OF APPROACH TO VETTING
TARGETS, YEAH, I'M SURE THE
CUTCHES ARE ALREADY DOING ALL OF
THAT BUT THEY CAN DO AS MUCH AS
THEY WANT BECAUSE IT ALL BOILS
DOWN TO ACTUALLY TESTING IT AND
I'VE LEARNED THAT THE HARD WAY,
TOO.
NTHANK YOU.
>> SURE.
>> YES, SIR NHI, FASCINATING,
FASCINATING TALK EMPLOY I WAS
STRUCK BY YOUR COMMENTS ON HOW
THE THERAPY AND PEWIC AGENTS ARE
SELECTING FOR CANCER THAT NO
LONGER EXPRESSES THE TARGET AND
SO, THAT MAKES LIFE REALLY
COMPLICATED FOR HOW YOU FOLLOW
THE EXAM BECAUSE IF YOU'RE
FOLLOWING THE PATIENT SO IF
YOU'RE USING PMSA, IS IT REALLY
THE CASES THAT THE GUYS FALLING
OFF YOUR KAPLAN MIER THEY GET
WORSE AND NEGATIVE OR THEY HAVE
NO EVIDENT OF PROGRESSION ON
PSMA, IF THAT'S THE CASE, FIEBD
AN ORTHOGONAL AGENT LIKE FDG AND
LOOK FOR DISCORDANCES?
>> YEAH, THAT'S RIGHT.
FDG HAS BEEN PROPOSED AS
SOMETHING TO USE AS SELECT
PATIENTS THAT WOULD NOT BE GOOD
CANDIDATES FOR THIS THERAPY.
I WOULDN'T GO THAT FAR BUT I
THINK THAT YEAH, WE NEED OTHER
WAYS TO IMAGE THEM EMPLOY SO WE
TRY TO HIT 2 TARGETS AT LEAST.
OR WE CAN BRING IN, YOU KNOW, I
DON'T KNOW MAYBE DIFFUSION
WEIGHTED WHOLE BODY EMR IMAGING,
SO THERE HAVE TO BE OTHER WAYS
OF FOLLOWING THEIR PEASHTS IF
YOU WANT TO FOLLOW THEM WITH
IMAGING RATHER THAN JUST LOOKING
AT THEIR PSA, BUT YEAH, THAT'S
KIND OF I THINK WHAT'S HAPPENING
IS THAT WE'RE JUST SELECTING AND
THE NEUROENDOCRINE PROSTATE
CANCER WHEN I FIRST LEARNED
ABOUT THAT ABOUT 10 YEARS AGO,
IT WAS SOMEBODY FROM CORNELL, I
CAN'T REMEMBER WAS TELLING--HE'S
A MEDICAL ONCOLOGIST AND HE SAID
THAT YEAH, WE'RE FINDING NOW
WITH SOME OF THESE NEWER AGENTS
LIKE [INDISCERNIBLE] AND PATES
ARE DEVELOPING THIS
NEUROENDOCRINE PHENOTYPE SO THE
CANCER, CANCER'S JUST, IT'S
UNBELIEVABLE, THERE'S THIS WHOLE
NEW FIELD CALLED WHAT IS IT
CANCER NEUROSCIENCE WHERE TUMOR
CELLS IN THE BRAIN GLIOMA WILL
ACTUALLY CONVINCE THEY'LL
CONVINCE NEURONS TO FEED THEM
GLUTAMATE AND THEY CONVINCE THE
NEURON TO PUT OUT LIKE A LITTLE
PSEUDOPOD OR SOMETHING AND IT'S
BASED ON, IT'S A 1 WAY SYNAPSE,
IT'S A FLUTA MITTURGIC SYNAPSE
ISSUES IT'S AN AMPA SYNAPSE AND
IF CANCER CAN DO THAT, RIGHT, I
MEAN HOW ARE YOU GOING TO--IT'S
JUST WAY SMARTER THAN I EVER
THOUGHT.
I THOUGHT THESE MAGIC BULLETS
WERE THE ANSWER WHICH IS WHY I
BECAME A CHEMIST BUT THERE'S A
LOT MORE TO IT AND I HOPE I LIVE
LONG ENOUGH TO SEE, MORE OF
THESE CHECK POINT INHIBITOR TYPE
RESULTS.
>> GREAT.
THANKS.
>> GOOD SEGUE TO MY QUESTION,
YOU KNOW YOU TALKED ABOUT THE
KAPLAN MEYERS FOR THE CHECK
BOOKS AND HOW HORIZONTAL THEY
WERE.
WHAT ARE YOUR THOUGHTS AROUND
THE ABILITY OF RADIATION THERAPY
TO INDUCE IMMUNE ACTIVATION THAT
CAN BE THEN EXPLOITED BY IMMUNE
THERAPIES.
>> YEAH, WE KNOW THAT'S
HAPPENING, THAT HAS NOT HAPPENED
IN ANY CLINICAL TRIALS THAT I
KNOW OF BUT IT'S LIKE A GIGANTIC
ABNORMALITIES SCOPAL EFFECT
WHICH IS SOMETHING THAT I
BELIEVE DOES OCCUR, I BELIEVE
THE RADIATION ONCOLOGIST
BELIEVES CAN COME AND GO EVERY
FEW YEARS BUT I THINK THAT YOU
DO STIR UP THE MICROENVIRONMENT
WITH THE RADIATION.
THERE'S OTHER THINGS CAN YOU
DOJ, TOO, SO 1 THING WE'RE
WORKING ON, WE'RE TAKING SOME OF
THESE FAP AGENT ANDS WE HAVE
OTHER AGENTS FOR MACROPHAGES AND
WE'RE JUST GOING TO WIPE OUT THE
WHOLE MICROENVIRONMENT AND SEE
WHAT HAPPENS AND IT HAS NO
COLLABORATORS, HEY, WHERE IS
EVERYBODY, RIGHT IN AND IT'S NOT
GOING TO BE ABLE TO GET THE
NUCLEOTIDES T-REGENTS OR
WHATEVER IT IS--I THINK THAT THE
MACROENVIRONMENT, THERE'S GOOD
MACROPHAGES AND BAD MACROPHAGES
BUT THERE'S WAY MORE BAD
MACROPHAGES, IN MY OPINION, THE
M2.
SO I THINK YEAH THERE'S A LOT OF
STUFF GOING ON IN THAT
MICROENVIRONMENT THAT WE'RE JUST
BEGINNING TO THINK ABOUT AND I
THINK THAT THE RADIATION WHETHER
IT'S EXTERNAL BEAM RADIATION OR
ALPHA PARTICLE OR WHATEVER, OR
INSITU RADIATION WILL BE HELPFUL
FOR THAT AND I THINK THAT THE
PDL 1 INHIBITOR IN THERE AND IT
WILL BE A BIT SYNERGISTIC AND
CANCER DOESN'T HAVE A LOT OF
T-CELLS IN ANY EVENT BUT MAYBE
YOU WOULD HAVE MORE IF YOU
DEPARTMENT HAVE THESE BAD ACTORS
IN THE MICROENVIRONMENT.
ALL RIGHT, THANK YOU VERY MUCH.
[ APPLAUSE ]