ERICH VOGT SYMPOSIUM
TRIUMF’S 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
• 1930s: Discovery of artificial isotopes, notably Iodine-131 and
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Tc99m
First treatment in 1939 with phosphorus-32
First treatment with iodine-131 in 1946
Gamma camera (Anger) and Rectilinear Scanner (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 beyond
Some Definitions
• SPECT: Single photon emission computed tomography
• Three dimensional images acquired from the single photon
emission produced by gamma emission decay
• Typical 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, …
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
generator
• BNL, 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”
Tucker and Richards
In part from http://www.bnl.gov/bnlweb/history/Tc-99m.asp
Single Photon Emitters in Oncology
111In
99mTc
Pentetreotide for neuroendocrine cancers
MDP Bone Scan
99mTc
Sulfur Colloid
Sentinel Node Detection
99mTc
Sestamibi
Breast Cancer Detection
Accelerator Produced Single Photon
Emitters
• Iodine-123
• Thyroid imaging
• Thyroid cancer detection
• Gallium-67
• Infection/inflammation imaging
• Indium-111
• Infection imaging, tumour imaging with peptides and antibodies
• Thallium-201
• Cardiac imaging
All made at TRIUMF…
99mTc
Production by Cyclotrons
• Concept proven by several authors in past 40 years at low
proton beam currents
• Beaver and Hupf, J Nucl Med 1971; 12:739-741
• Lagunas-Solar et al., Appl Radiat Isot 1991; 42:543
• Levkovskii N et al. 1991
• Scholten et al., Appl Rad Isot 1999; 6-80
J Nucl Med 1971; 12: 739-741
The Technology
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 infrastructure
Vision
• Paradigm well suited to central radiopharmacies
• Cyclotron capability can be tailored to market
• Multiple cyclotrons provide redundancy
• Synergy between PET & SPECT
• Utilize existing PET cyclotrons to diversify Tc99m supply
• More cyclotrons will facilitate the transition of nuclear
medicine imaging infrastructure, from SPECT to PET
• Complementary to LINAC/other sources of
• Generators freed up for remote areas
99Mo
The Technology
• Daily irradiation of Tc99m
• Regional/Supraregional distribution
• 6-hour half-life
• Can be combined with 18F-FDG
distribution
• Shipping by road or air
• Processing and release currently
takes ~2 h
Canadian Cyclotron Infrastructure
• 24 Cyclotrons in Canada
• 6 in Vancouver
• 4 in Toronto
• 3 in Montreal
• 2 each in Hamilton, Edmonton, Sherbrooke
• 1 in Winnipeg, London (ON), Ottawa, Halifax,
Saskatoon
• 3 new cyclotrons planned or purchased
• Thunder Bay, St-John’s, Vancouver
Worldwide: 889 cyclotrons in 2013
June 3, 2014
Achieving Large Scale Production, Distribution, and
Commercialization of Tc-99m
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Determinants of Tc-99m yield
• Proton beam current
• Expressed in µA (microampers)
• Proton beam energy
• Expressed in MeV (megaelectron-volts)
• Production starts around 8-10 MeV, peaks at 15 MeV
• Higher energy means thicker proton penetration = higher yield
• Examples of theoretical yields (6 h runs)
• 130 µA, 16.5 MeV (GE cyclotron): 4.9 Ci
• 160 µA, 16.5 MeV (GE cyclotron): 6.1 Ci
• 300 µA, 18 MeV (TR19 cyclotron): 15.4 Ci
• 300 µA, 20 MeV (TR24 cyclotron): 18.7 Ci
• 500 µA, 20 MeV (TR24 cyclotron): 31.1 Ci
• 500 µA, 24 MeV (TR24 cyclotron): 39.2 Ci
• Practical net yields 85-95% of theoretical
Preclinical images – 99mTc-MDP (bone scan)
Mouse injected 24 h after production
Will Other Modalities Replace 99mTc?
The Supply of Medical Radioisotopes, Nuclear Energy Agency, OECD, 2011
How TRIUMF helped other PET programs
in Canada
• Started the UBC PET program for neuroimaging
• Sent radioisotopes to Edmonton to help them start their
PET program on cancer imaging
• Allowed BCCA to setup 18F-FDG production at TRIUMF to
ship isotopes for cancer imaging
• Helped the Ottawa Heart Institute setup their 82Sr/82Rb
generator which started their cardiac PET program
• Set up 64Cu production at Sherbrooke
Replacement of 99mTc with PET studies
• 17% of nuclear medicine studies are bone scans
• Can be replaced with 18F-NaF
• 56% myocardial perfusion studies
• Can be replaced with 82Rb, 18F-Flurpiridaz, 18Fphosphonium cations
99mTc
Bone Scan
18F
PET Scan
Myocardial Imaging with PET
Maddahi J., J Nucl Cardiol 2012; 19, Suppl 1, S30-7
13N-NH
3
82RbCl
– Courtesy, University of Ottawa
and 18F-FDG for viability
Cancer Imaging Targets BCCA/TRIUMF
Future radiotracers for cancer imaging
h
l
s
t
24 hr
68Ga-bradykinin
68Ga
imaging
CA-IX imaging
48 hr
72 hr
5 days
7 days
Radiolabeled antibodies
18F-bombesin
imaging
Erich Vogt - Bridging the gap between
Physics and Medicine
Pilfered from http://vogt.physics.ubc.ca/vogt/gallery/
TRIUMF’s Contributions for the Future
• Continue developments in radiochemistry and imaging
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probes
Secure radioisotope supply for British Columbia for all
nuclear medicine radioisotopes
Development of alpha emitter radionuclide therapy
Development of exotic medical radioisotopes
Expansion of proton therapy?