erich vogt symposium triumf’s current and future impact in nuclear medicine and molecular imaging...
TRANSCRIPT
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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
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A Brief History of Nuclear Medicine• 1930s: Discovery of artificial isotopes, notably Iodine-131 and
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
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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, …
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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”
In part from http://www.bnl.gov/bnlweb/history/Tc-99m.asp
Tucker and Richards
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Single Photon Emitters in Oncology
99mTc MDP Bone Scan
99mTc Sulfur Colloid Sentinel Node Detection
111In Pentetreotide for neuroendocrine cancers
99mTc Sestamibi Breast Cancer Detection
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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…
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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
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The Technology
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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
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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 99Mo• Generators freed up for remote areas
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•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
The Technology
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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
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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
June 3, 2014Achieving Large Scale Production, Distribution, and
Commercialization of Tc-99m 14
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Preclinical images – 99mTc-MDP (bone scan)Mouse injected 24 h after production
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Will Other Modalities Replace 99mTc?
The Supply of Medical Radioisotopes, Nuclear Energy Agency, OECD, 2011
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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
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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, 18F-
phosphonium cations
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99mTc Bone Scan 18F PET Scan
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Myocardial Imaging with PET
Maddahi J., J Nucl Cardiol 2012; 19, Suppl 1, S30-7
13N-NH3 and 18F-FDG for viability
82RbCl – Courtesy, University of Ottawa
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Cancer Imaging Targets BCCA/TRIUMF
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Future radiotracers for cancer imaging
24 hr 48 hr 72 hr 5 days 7 days
sl
th
68Ga-bradykinin imaging Radiolabeled antibodies
68Ga CA-IX imaging18F-bombesin imaging
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Erich Vogt - Bridging the gap between Physics and Medicine
Pilfered from http://vogt.physics.ubc.ca/vogt/gallery/
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TRIUMF’s Contributions for the Future
• Continue developments in radiochemistry and imaging 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?