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 • • • • • • • • 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 14 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 • • • • 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?