Nuclear Medicine Division

1. CANADA’S NATIONAL LABORATORY FOR PARTICLE AND NUCLEAR PHYSICS Owned and operated as a joint venture by a consortium of Canadian universities via a contribution through the National Research Council Canada LABORATOIRE NATIONAL CANADIENPOUR LA RECHERCHE EN PHYSIQUE NUCLÉAIRE ET EN PHYSIQUE DES PARTICULES Propriété d’un consortium d’universités canadiennes, géré en co-entreprise à partir d’une contribution administrée par le Conseil national de recherches Canada Nuclear Medicine Division JM POUTISSOU ACOT 13 March 2009

2. Nuclear Medicine Division • The Science we do • Our people power • Our infrastructure • Our goals • A canadian vision

3. Mission • The mission of TRIUMF Nuclear Medicine Division is to perform research and development for the production of radioisotopes with potential applications in physical and biomedical research, to prepare certain commercially unavailable radioisotopes for distribution to researchers, to design and synthesize radiotracers with optimal properties for imaging biological targets and to develop novel tracer imaging systems. • In conjunction with this mission, the group also performs service irradiations and explores opportunities for new radioisotopes applications. • The program is focused very strongly on making use of the unique particle beams from the TRIUMF accelerators and of its radioisotope production facilities. • The group acts as a support group for the research community in the use of modern tools associated with the production and detection of radiotracers produced at TRIUMF and as a consulting team to potential commercial providers of isotopes or other such technologies as employed by the program, under TRIUMF licensing agreements. • The program includes also projects making use of particles beams directly ( like proton therapy , proton irradiations,..)

4. Areas of Research where TRIUMF Excels Radionuclide Research Molecular Imaging Radiotracers Technologies /Detectors /computing Radiochemistry Accelerators

5. The Engine: TRIUMF Laboratory • The cars • Academia: Well funded Pacific Parkinson’s Research Centre • Research Institute: Emerging Research Program in Functional Imaging at the BC Cancer Agency • Industry: Interest by MDS-Nordion in Research and development

6. Science with academia: UBC • Pacific Parkinson Research Centre • UBC Psychiatry

10. UBC PET Program • Complications of PD: Inverse relationship between dopamine (DAT) expression and dopamine turnover (published) and as a corollary, evidence that reduced DAT expression is associated with increased risk of dyskinesias (Neurology, under revision). • No difference between depressed and non-depressed PD subjects in amphetamine-induced DA release. • Mood disorders: Preliminary results suggest that increased dopaminergic activity in mania is due to reduced dopamine transporter with consequent failure of uptake of dopamine into presynaptic neuron.

11. Continued • Placebo effect: Placebo-induced DA release in both the putamen and the ventral striatum was seen only when subjects were told there was a 75% probability of receiving active drug (levodopa) and not at 25, 50 or 100%. • Studies on the role of conditioning are underway and suggest that, as expected, administration of active drug in a ritualized setting leads to enhancement of the behavioural response to a placebo administered in the same setting. • Gambling: A pilot study of hedonic stimuli (flavoured drinks) to elicit DA release.

14. Support- >$4.4M/year 4004 Wesbrook Mall Vancouver, B.C. Canada V6T 2A3 Tel: 604 222-1047 Fax: 604 222-1074 www.triumf.ca Pacific Parkinson’s Research Institute PARF BCKDF

15. Science with Health Institutes: BCCA • LS93 18F-Fluoroestradiol PET/CT guided fulvestrant therapy for patients with recurrent or metastatic breast cancer F.Benard (BCCA),M.Adam(TRIUMF),M.Vulcovic(BCCA) • Assess the potential of [18F]FES PET/CT imaging to predict the benefit of administering fulvestrant in women with recurrent or metastastic breast cancer who have progressed following treatment with aromatase inhibitors and/or tamoxifen. • 1) High [18F]FES uptake at the baseline scan in known tumor sites is predictive of clinical benefit to fulvestrant therapy, while low [18F]FES uptake in some or all active tumor sites is predictive of fulvestrant therapy failure • 2) Limited blockage/downregulation of [18F]FES uptake after 3 months of fulvestrant therapy is predictive of treatment failure. • To assess these hypotheses we will conduct a prospective phase II cohort study to determine whether [18F]FES uptake at baseline and/or after reaching pharmacological steady-state of fulvestrant therapy can predict clinical benefit to this drug. • The accrual plan is 100 patients over 2 years.

16. Science (BCCA) • FES is being developed at TRIUMF by Milan Vuckovic and M.Adam’s team for testing the quality of the product. • The full Trial has been funded by NIH and should proceed at BCCA when their production facility will be operational.

17. Science with Health Institutes: BCCA • LS 74: Principal investigators D.Yapp (BCCA) and Mike Adam(TRIUMF) • EF5 Marking agent for tumor Hypoxia in Lung cancer • Produced by M.ADAM at TRIUMF • 3 Patients accrued so far for pre and post chemio therapy treatment scanning with EF5 produced at TRIUMF • Evaluation after 6 Patients • Study funded by Roche

19. Science with Nordion • LS 85 and LS90 With MDS-Nordion Vancouver • NSERC Collaborative Research and Development Award (3Year/$100K/y) with matching funds from MDS Nordion • UBC Chemistry (C.Orvig), TRIUMF (M.Adam), MDS-Nordion ( D.Wester, C Ferreria) • Enabling Technologies for Metallic Radioisotopes in Nuclear Medicine (LS90) • Investigate the design possibilities for target-specific bioconjugates for 68Ga and/or 111In as novel brain, heart, tumour and cardiovascular plaque imaging agents • provide a new generation of compounds for radioimaging • develop new chelation chemistry of Ga and In that will lay the groundwork for further advances in molecular imaging. • Post doc and Student hired • Similar with 64Cu (LS 85) • C. Ferreira(MDS-Nordion) spokesperson

20. New MHESA Radio-chem lab

21. The Team

22. Nuclear Medicine Division Nuclear Medicine Division J.M. Poutissou (Interim) Accelerator Division LSPEC • MDS Nordion • R/D • D. Wester • C. Ferreira Operations R. Ruegg Deputy M. Adam Safety/Training/Documentation TBA Radio Chemistry M. Adam Targetry/Methodolgy New Lab/GMP K. Buckley CFI T. Ruth Cyclotron Operations C. Hoehr R/D M. Adam - W. English - L. Graham - V. Barreras (BCCA) Production S. Jivan Camera Support • M. Dodd • Post Doc (TBA) • New TBA • J. Lu • J. Inkster • Students • Students - [G. Sheffer] (Detector Group) UBC BCCA • - J. Greene • C. Takhar • - V. Barreras • [TBA] • [M. Vuckovic] • [Y. Rozen]

23. PET director (on leave from Sept 01/08 to Aug 31/09)PPRC director AJ Stoessl V Sossi PET acting directorAJ Stoessl Faculty P.I. using PET R de la Fuente-Fernandez(UBC – PPRC) D. Doudet (UBC Medicine) C Mackintosh (UBC- Cellular and Physiological Sciences) W Martin (UoA – Neurology) M Martinez (UBC Chem Eng) S Reinsberg (UBC Phas) V Sossi (UBC Phas) AJ Stoessl (UBC PPRC) Z Wszolek (Mayo Clinic, Jacksonville, Florida) L Yatham (UBC Psychiatry A Young (UBC- Psychiatry Katie Dinelle Lab Management Staff/Student supervision Scanner scheduling Carolyn English PET Technologist Scanner scheduling Ryan Thomson System Administrator Salma Jivan Chemistry development Scanner scheduling Jennifer Green Routine Chemistry/Scheduling Stephan Blinder Scanner sofware Maintenance Student Supervision Physics Experiments Caroline Williams PET Technologist Christine Takhar Routine Chemistry Nasim Vafai Software Management Siobhan McCormick Small animal imaging and human image analysis Jian-Ming Lu Precursor Development Rick Kornelsen Small animal imaging, animal handling and small animal image analysis Individual project related fellows, coordinators, Postdocs and students Henry Ngo Co-op student

24. The tools: Infrastructure • Tr13 cyclotron • “old” Radiochemistry laboratories • New MHESA R/D laboratory with Nordion • Pet imaging centre at UBC (director V.Sossi) • HRRT • Advance (GE) whole body • MicroPET • Future large Animal imaging laboratory

25. Work plan Short term ( 2009-2010): • Consolidate existing radiotracers production and optimize their yields, especially for 11C based tracers. • Understand the production yield difference of the East versus West port of the TR13. • Understand the production yield for 11C from niobium targets ( Nb tube vs block) • Optimize the conversion efficiency for CH4 to methyliodide • Evaluate the production of CO2- MEI vs CH4-MEI • QA metric: delivering more than 95% of scheduled scans • Recommission the “ADVANCE” GE camera • Renovation • Calibration • MRO support • Initiate R/D program associated with the CDR grant on metallic tracers • Develop a the RCRC MHESA laboratory. • Prepare second CR proposal with MDS Nordion • Integrate proton therapy and proton irradiation into the division • Prepare a plan for extending the support provided to the BCCA nuclear medicine group for the production 18F at TRIUMF during the period before and after installation of their own production facilities. • 6) GMP issues, may become 0): Design new facilities for New building or renovate Chemistry annex facilities. This will depend on the success of the CFI proposal and or the provincial government funding for the new building

27. Work Plan Mid Term: ( 2010-2012) • 1) Start building a national network with or without CFI support. • 2) Launch new collaborations: • Cross cancer(Edmonton),BCCA ,TRIUMF • Calgary, BCCA, TRIUMF. • MDS Nordion • 3) Explore new avenue with Genome BC / GEHealthcare / P-Cure/U.Calgary • 4) Establish an imaging centre at the UBC animal care facility

28. Infrastructure requirements • Commission TR13 enclosure • Stop gap measure, before enclosing the cyclotron in a proper vault in a new Nuclear Medicine building. • Commission Advance camera • More reliable long term full body scanning ability • Build new RCRC Lab • State of art radiochemistry lab with new nuclear ventilation and hot cells for R&D • Exploit Microfluidics technologies • Shorter reaction time and better specific activities

29. Experimental Setup Microscope Syringe Pumps Monitor and VCR Chip in Chip Holder Collection Vial Chip Syringe Pumps CH3I/CH3CN solution Precursor Solution CCD Camera Hot plate S. Haroun, SFU

30. 11C-Raclopride – mfluidic approach Hot off the press 11C-raclopride 11CH3I No detectable Mass peak!

31. 11C-Raclopride – Traditional Method

32. Personnel requirements • Search for Head of Division • Add Radio-chemist • Post Doctoral fellows • Students

33. Challenges for Program • Meet the demands of the existing program that is growing rapidly – well funded projects, need for facilities that meet regulatory oversight. • Be in position to meet the needs of emerging programs wanting access to molecular imaging. • Support a national effort to work cooperatively in molecular imaging.

34. CANADA’S NATIONAL LABORATORY FOR PARTICLE AND NUCLEAR PHYSICS Owned and operated as a joint venture by a consortium of Canadian universities via a contribution through the National Research Council Canada LABORATOIRE NATIONAL CANADIENPOUR LA RECHERCHE EN PHYSIQUE NUCLÉAIRE ET EN PHYSIQUE DES PARTICULES Propriété d’un consortium d’universités canadiennes, géré en co-entreprise à partir d’une contribution administrée par le Conseil national de recherches Canada National CFI Proposalon Radiotracer Development TJ Ruth 09 May 2008

35. Mechanisms for Inclusion • National CFI – Natural vehicle for funding • CAMINET – Driver for the future Institutions CAMINET Canadian Collaborators CFI CECRs Industry

36. UBC/TRIUMF -Lead Cross Cancer Institute McMaster University MNI/McGill University Ottawa Heart Institute Université de Sherbrooke BC Cancer Agency Dalhousie University Lawson Health Research Institution(London, ON) Sunnybrook (Toronto) Thunder Bay (Ontario) Université de Montréal University Health Network (PMH) University of Manitoba The 14 Partnering Institutions Active Cyclotron Based Programs Establishing Cyclotron Programs Terry Fox Research Institute

37. Conclusions • Nuclear Medicine Division has been created to elevate the status of this effort from peripheral to core mandate of the laboratory • Nuclear Medicine division builds on a small but talented team of world recognized PET experts. • Nuclear Medicine division has access to world class accelerator, nuclear physics and detector technologies expertise on site. • Nuclear Medicine group imbedded in collaborations with academia, health institutes and industry. • Nuclear Medicine needs updated infrastructure to continue and grow • Nuclear Medicine needs updated infrastructure to attract top quality people.

38. From now to a bright future • Need strong endorsement of the vision for Nuclear Medicine at TRIUMF from ACOT • Need strong support for the next Five year plan to attract top quality personnel • Need BC support for infrastructure

39. 4004 Wesbrook Mall Vancouver, B.C. Canada V6T 2A3 Tel: 604 222-1047 Fax: 604 222-1074 www.triumf.ca Thanks to the whole NuMed team for helping with the content of the presentation