TRIUMFS CURRENT AND FUTURE IMPACT IN NUCLEAR MEDICINE AND MOLECULAR IMAGING OF CANCER Dr François Bénard BC Leadership Chair in Functional Cancer Imaging A Brief History of Nuclear Medicine ID: 254633
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ERICH VOGT SYMPOSIUMTRIUMF’S CURRENT AND FUTURE IMPACT IN NUCLEAR MEDICINE AND MOLECULAR IMAGING OF CANCER
Dr. François BénardBC Leadership Chair in Functional Cancer ImagingSlide2
A Brief History of Nuclear Medicine
1930s: Discovery of artificial isotopes, notably
Iodine-131 and Tc99mFirst treatment in 1939
with phosphorus-32First treatment
with
iodine
-131 in 1946
Gamma camera (Anger) and
Rectilinear
S
canner (
Cassen
) in 1950s
Thyroid
imaging
1950-1960
Liver
/spleen scanning,
bone
imaging
,
brain
tumour
localization
1960-1970s
Positron
emission
tomography
in 1970s+ for
brain
imaging
Cardiac
imaging
1980s+
Cancer
imaging
in the 1990s and
beyondSlide3
Some DefinitionsSPECT: Single photon
emission computed tomographyThree dimensional images acquired
from the single photon emission produced by gamma
emission decayTypical isotopes: Tc-99m, In-111, Tl-201, I-123,…
PET: Positron
emission
tomography
Three
dimensional
images
acquired
from
the dual photon
emission
produced
by the annihilation of a positron
Typical
isotopes: C-11, F-18, Ga-68, O-15, Rb-82, …Slide4
Technetium-99m, the Medical Isotope of the 20th Century
Element
43
discovered by Carlo Perrier and Emilio Segrè in 1936
Technetium-99
discovered
by Seaborg and Segrè at the Berkeley Radiation
Laboratory
BNL, 1950s: Tucker and Green developed the first
99Mo/99mTc generatorBNL, 1960: Powell Richards, presented the first paper on the generator.Richards met with Paul Harper on the flight to Rome and spent the flight “extolling the merits of 99mTc”
In part from http://www.bnl.gov/bnlweb/history/Tc-99m.asp
Tucker and RichardsSlide5
Single Photon Emitters in Oncology
99m
Tc MDP Bone Scan
99m
Tc Sulfur Colloid
Sentinel Node Detection
111
In
Pentetreotide
for neuroendocrine cancers
99mTc Sestamibi Breast Cancer DetectionSlide6
Accelerator Produced Single Photon EmittersIodine-123
Thyroid imagingThyroid cancer detectionGallium-67Infection/inflammation imagingIndium-111Infection imaging, tumour imaging with peptides and antibodies
Thallium-201Cardiac imagingAll made at TRIUMF…Slide7Slide8
99m
Tc Production by CyclotronsConcept proven by several authors in past 40 years at low proton beam currentsBeaver and
Hupf, J Nucl Med 1971; 12:739-741Lagunas-Solar et al.,
Appl Radiat Isot 1991; 42:543
Levkovskii
N et al. 1991
Scholten
et al.,
Appl
Rad
Isot 1999; 6-80J Nucl Med 1971; 12: 739-741Slide9
The TechnologySlide10
Can Cyclotrons help prevent isotope shortages?Distribution model established for
18F-Fluorodeoxyglucose (110 min half-life)Mixed model possible for 18F (1 h irradiation) and 99mTc production (3-6 h irradiations)Take advantage of existing infrastructureSlide11
VisionParadigm well suited to central
radiopharmaciesCyclotron capability can be tailored to marketMultiple cyclotrons provide redundancySynergy between PET & SPECTUtilize existing PET cyclotrons to diversify Tc99m supplyM
ore cyclotrons will facilitate the transition of nuclear medicine imaging infrastructure, from SPECT to PETComplementary to LINAC/other sources of 99MoGenerators freed up for remote areasSlide12
Daily irradiation of Tc99mRegional/Supraregional distribution6-hour half-lifeCan be combined with 18F-FDG distribution
Shipping by road or airProcessing and release currently takes ~2 hThe TechnologySlide13
Canadian Cyclotron Infrastructure24 Cyclotrons in Canada
6 in Vancouver4 in Toronto3 in Montreal2 each in Hamilton, Edmonton, Sherbrooke1 in Winnipeg, London (ON), Ottawa, Halifax, Saskatoon 3 new cyclotrons planned or purchased
Thunder Bay, St-John’s, Vancouver
Worldwide: 889 cyclotrons in 2013Slide14
Determinants of Tc-99m yieldProton beam current
Expressed in µA (microampers)Proton beam energyExpressed in MeV (megaelectron-volts)Production starts around 8-10 MeV, peaks at 15 MeV
Higher energy means thicker proton penetration = higher yieldExamples of theoretical yields (6 h runs)130 µA, 16.5 MeV (GE cyclotron): 4.9 Ci160 µA, 16.5 MeV (GE cyclotron): 6.1 Ci
300 µA, 18 MeV (TR19 cyclotron): 15.4 Ci300 µA, 20 MeV (TR24 cyclotron): 18.7 Ci500 µA, 20 MeV (TR24 cyclotron): 31.1 Ci500 µA, 24 MeV (TR24 cyclotron): 39.2 Ci
Practical net yields 85-95% of theoretical
June 3, 2014
Achieving Large Scale Production, Distribution, and Commercialization of Tc-99m
14Slide15Slide16Slide17Slide18Slide19Slide20
Preclinical images – 99mTc-MDP (bone scan)Mouse injected 24 h after productionSlide21
Will Other Modalities Replace 99mTc?
The Supply of Medical Radioisotopes, Nuclear Energy Agency, OECD, 2011Slide22
How TRIUMF helped other PET programs in CanadaStarted the UBC PET program for neuroimaging
Sent radioisotopes to Edmonton to help them start their PET program on cancer imagingAllowed BCCA to setup 18F-FDG production at TRIUMF to ship isotopes for cancer imagingHelped the Ottawa Heart Institute setup their 82Sr/82
Rb generator which started their cardiac PET programSet up 64Cu production at SherbrookeSlide23
Replacement of 99mTc with PET studies17% of nuclear medicine studies are bone scans
Can be replaced with 18F-NaF56% myocardial perfusion studiesCan be replaced with 82Rb,
18F-Flurpiridaz, 18F-phosphonium cationsSlide24
99m
Tc Bone Scan
18
F PET ScanSlide25
Myocardial Imaging with PET
Maddahi J., J Nucl
Cardiol 2012; 19, Suppl 1, S30-7
13
N-NH
3
and
18
F-FDG for viability
82
RbCl – Courtesy, University of OttawaSlide26
Cancer Imaging Targets BCCA/TRIUMFSlide27
Future radiotracers for cancer imaging
24
hr
48
hr
72
hr
5 days 7 days
s
l
t
h
68
Ga-bradykinin imaging
Radiolabeled antibodies
68
Ga
CA-IX imaging
18
F-bombesin imagingSlide28
Erich Vogt - Bridging the gap between Physics and Medicine
Pilfered from http://vogt.physics.ubc.ca/vogt
/gallery/Slide29
TRIUMF’s Contributions for the FutureContinue developments in radiochemistry and imaging probesSecure radioisotope supply for British Columbia for all nuclear medicine radioisotopes
Development of alpha emitter radionuclide therapyDevelopment of exotic medical radioisotopesExpansion of proton therapy?