Canada’s National Laboratory for Particle and Nuclear Physics
Laboratoire national canadien pour la recherche en physique nucléaire et en physique des particules
Nuclear Medicine:Vision and Goals
PPAC, Nov. 1st, 2012
Paul Schaffer | Head, Nuclear Medicine | TRIUMF
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Owned and operated as a joint venture by a consortium of Canadian universities via a contribution through the National Research Council Canada
Propriété d’un consortium d’universités canadiennes, géré en co-entreprise à partir d’une contribution administrée par le Conseil national de recherches Canada
OHF18
Vision• Vision: TRIUMF Nuclear Medicine willVision: TRIUMF Nuclear Medicine will
emerge as a Centre of Excellence in all aspects of medical isotope researchaspects of medical isotope research.
• Three facets of program:– We will attract and train world-class HQP– We will address unmet needs throughWe will address unmet needs through
innovation We will deliver world class science– We will deliver world-class science
11/6/2012 2TRIUMF Nuclear Medicine
Nuclear Medicine at TRIUMF: Our Focus
TargetDev.
IsotopeProd.
Tracer Prod.
(Pre)clinicalStudies
DetectorDev.
CyclotronDev.
Core competenciesCore competencies
Our Competencies…Our Focus:• Define our research activities• Define our research activities• Dictate our infrastructure upgrades• Focus our hiring plang p• Drive our future growth/goals
Scientific Focus: RadiometalsTRIUMF Nuclear Medicine
Scientific Focus: Radiometals
2010-2015 5YP Goals
• Upgrade and transformation of infrastructurepg…a need for facilities that meet regulatory oversight
• National network for radiotracer developmentNational network for radiotracer development• Focused research and development of microfluidics• Expanded cyclotron targetry for PET isotopes• Expanded cyclotron targetry for PET isotopes• Innovative techniques for mining novel radionuclides,
especially from the new e linac accelerator proposedespecially from the new e-linac accelerator proposed at TRIUMFStrengthen existing partnerships• Strengthen existing partnerships
11/6/2012 TRIUMF Nuclear Medicine 4
5YP Goals: Infrastructure Upgradesg
• Upgrade and transformation of infrastructurepg…a need for facilities that meet regulatory oversight
• National network for radiotracer developmentNational network for radiotracer development• Focused research and development of microfluidics• Expanded cyclotron targetry for PET isotopes• Expanded cyclotron targetry for PET isotopes• Innovative techniques for mining novel radionuclides,
especially from the new e linac accelerator proposedespecially from the new e-linac accelerator proposed at TRIUMFStrengthen existing partnerships• Strengthen existing partnerships
11/6/2012 5TRIUMF Nuclear Medicine
Transition to GMP facilityy
Process transition to GE ASUs:Process transition to GE ASUs:3 ‘new’ tracers: 11C-MRB, 11C-DASB
and 11C-PBR28Transition Legacy Tracers: 11C-Raclopride, 11C-PMP, 11C-DTBZSpec. act.: > 2000 Ci/mmolSpec. act.: 2000 Ci/mmol
New Directions:1. Exploration of the role of the serotonergic system in PD
a. Disease origin (Braak hypothesis)g ( y )b. Treatment related complications
2. Increased emphasis on genetic PD
63. Establishment of collaborations with HIV, brain trauma and
MS research groups
New Offices
• 4 offices 14 cubicles4 offices, 14 cubicles• Conference room• 8 additional desks
il blavailable• 5 people in 3 offices at
FP Innovations
Motivation: Team building, Space optimization, Future Growth
11/6/2012 7TRIUMF Nuclear Medicine
g p p
Joint TRIUMF/NordionMHESA laboratoryMHESA laboratory
• Joint TRIUMF/Nordion facility for applied research• Lab commissioning underway• Lab commissioning underway
8• Risks: Resources scarce for continued upgrades
Improving TRIUMF Facilitiesg
• Joint TRIUMF/Nordion effort with contributions from NRCanJoint TRIUMF/Nordion effort with contributions from NRCan
Wet ChemLabLab
In vitroLab
RadiochemLab
Target Lab
Anal.Lab
11/6/2012 9
Upcoming effortTRIUMF Nuclear Medicine
Core Program: Improving/Expanding InfrastructureExpanding Infrastructure
Centre for Comparative Medicine (BC P li i l R h C ti )Preclinical Research Consortium)- Collaborative hub- TRIUMF to make tracers- TRIUMF to make tracers
New transfer line
New VECTor PET/SPECT/CT-funded by CFI – LOF (V. Sossi)
delivery Q2/2012New transfer lineto CCM
imaging facility
- delivery Q2/2012
5YP Goals: A National Network
• Upgrade and transformation of infrastructurepg• National network for radiotracer development• Focused research and development of microfluidicsFocused research and development of microfluidics• Expanded cyclotron targetry for PET isotopes• Innovative techniques for mining novel radionuclides• Innovative techniques for mining novel radionuclides,
especially from the new e-linac accelerator proposed at TRIUMFat TRIUMF
• Strengthen existing partnershipsa need for facilities that meet regulatory oversight• …a need for facilities that meet regulatory oversight
11/6/2012 11TRIUMF Nuclear Medicine
Program Reach: Nationalg
• 2011 NCE application submitted through Lawson: Not funded
• Refocus with NRCan: NISP and ITAP (TRIUMF as lead institution)• Use alternative 99mTc production to drive national interaction
• BC SK ON NS
126 November 2012 TRIUMF Nuclear Medicine
BC, SK, ON, NS• Interface with MITNEC for clinical trials
Program Reach: Internationalg
• Goal: grow TRIUMF Nuc. Med. reputation outside CanadaI t ti ith th i t t• Interactions with the private sector
• Nordion (our closest partner, MHESA, NSERC CRD)• GE Global Research (NY),GE Global Research (NY), • GE Healthcare, tracers (Amersham, UK)• GE Healthcare, cyclotrons (Uppsala, SWE)• GE Healthcare, academic support (Canada)
• IAEA Coordinated Research Project (TRIUMF, April 2012)A l t b d Alt ti t N HEU d ti f- Accelerator-based Alternatives to Non-HEU production of 99Mo/99mTc
• Interactions with other labs- SOREQ (Israel), Yale (Dr. Yu-Shin Ding visiting scholar)
• Upcoming retirements will influence interactions• Communications office (T Meyer) is crucial for this
Private Sector Interactions
Goal: to enable radiometal incorporation onto large mol. wt. di tradiotracers
Work with Nordion, UBC (funded by NSERC CRD)
M. Adam PI, collaborating with C. Orvig, D. Wester, othersHQP: 2 students 2 PDFsHQP: 2 students, 2 PDFs
14
Radiolabelled Amino Acids for Oxidative Stress Imagingfor Oxidative Stress Imaging
Goals: To produce 11C and 18F amino acid analoguesEstablish proof of feasibility showing increased uptakeEstablish proof of feasibility showing increased uptake with increased amino acid transporter function
15
Stated Goals in the 5YP
• Upgrade and transformation of infrastructurepg• National network for radiotracer development• Focused research and development of microfluidicsFocused research and development of microfluidics• Expanded cyclotron targetry for PET isotopes• Innovative techniques for mining novel radionuclides• Innovative techniques for mining novel radionuclides,
especially from the new e-linac accelerator proposed at TRIUMFat TRIUMF
• Strengthen existing partnershipsa need for facilities that meet regulatory oversight• …a need for facilities that meet regulatory oversight
11/6/2012 TRIUMF Nuclear Medicine 16
Microfluidics Research with SFU
Shifti f f i fl idi t i d l t• Collaboration with Paul Li (SFU)• Shifting focus from microfluidic to microdroplet
11C-Raclopride results:•Yields: 2 0 5 1 % with abacus
full loop•Yields: 2.0 – 5.1 % with abacus•Improved to 26.4% with full loop chip•Room for improvement
• Use of magnetic particles, I- +N (CH3)3-Si-Fe3O4
11/6/2012 17TRIUMF Nuclear Medicine
Microfluidics Research with SFU
Use of magnetic particles, I- +N (CH3)3-Si-Fe3O4 to capture 18F-
18F- in H2O
Collaboration with Paul Li (SFU)
Subsequent steps for radiolabelingFuture direction: Radiometals, Macromolecular labeling
11/6/2012 18TRIUMF Nuclear Medicine
, g
Genome BC: Antisense PET
• $0.16M for 1 year between TRIUMF/UBC/BCCA• NCE granted for 2nd year• Goal: in effect, is to image gene expression levels g g p
related to disease
CPP PNAF-18 / optical dyes
R di l (f )Signal
GCPP PNA
HIV Tatpeptide Anti-HER2
Radiometals(future)Generator
peptide
11/6/2012 19
4T1 (ERBB2 +ve)cells showing uptake
Stated Goals in the 5YP
• Upgrade and transformation of infrastructurepg• National network for radiotracer development• Focused research and development of microfluidicsFocused research and development of microfluidics• Expanded cyclotron targetry for PET isotopes• Innovative techniques for mining novel radionuclides• Innovative techniques for mining novel radionuclides,
especially from the new e-linac accelerator proposed at TRIUMFat TRIUMF
• Strengthen existing partnershipsa need for facilities that meet regulatory oversight• …a need for facilities that meet regulatory oversight
11/6/2012 TRIUMF Nuclear Medicine 20
NRCan: NISP to ITAPGoal: Commercialize 99mTc AlternativeGoal: Commercialize 99mTc Alternative
•Make 100Mo coating•Suitable for 16-19 MeV / 150 – 300 μA
100Mo Target
Cyclotron Modifications
100Mo Recycle
91% of MoO4 recoveredNeed to reduce back
to Mo(s)
•Upgrade cyclotrons (by collaborators)•Design & build solid
I di i
y
100Mo(p,2n)99mTcShow purity-% of non 100Mo isotopes
dictates other Tc
target stations (x3)•Design & build transfer systems (x3)
Irradiation ParametersRegulatory
dictates other Tc-Impurities/patient dose Established with
A. Celler (UBC):16-19 MeV optimal
Purificationof 99mTcO4
-
Celler et al. Phys. Med. Biol. 2011, 56, 5469
99mTc produced at all partner sites
•Method developed•Method developed•Module assembled
•Distribute to 3 collaborators Sept’11
Metal Salt Targets - CHRPg
Goal: Enable radiometal production – in solution• Allow cyclotron centres to obtain radiometal isotopes without
substantial infrastructure upgrades• Standard water target with metal salt in solution• Standard water target with metal salt in solution• First experiments: 94Mo(p,n)94mTc - published• Additional work to understand system (pressure solubility yields)Additional work to understand system (pressure, solubility, yields)• CHRP funded (joint with BCCA) to study: 89Zr, 68Ga, 44Sc, 86Y
11/6/2012 22C. Hoehr et al. Appl. Rad. Isotop. 2012, 70, 2308
Stated Goals in the 5YP
• Upgrade and transformation of infrastructurepg• National network for radiotracer development• Focused research and development of microfluidicsFocused research and development of microfluidics• Expanded cyclotron targetry for PET isotopes• Innovative techniques for mining novel radionuclides• Innovative techniques for mining novel radionuclides,
especially from the new e-linac accelerator proposed at TRIUMFat TRIUMF
• Strengthen existing partnershipsa need for facilities that meet regulatory oversight• …a need for facilities that meet regulatory oversight
11/6/2012 TRIUMF Nuclear Medicine 23
Innovative Techniques/Novel Medical IsotopesIsotopes
• Targeted therapy using alpha emitting radionuclidesg py g p g• Issues to resolve:
i) Lack of access to suitable quantities of thei) Lack of access to suitable quantities of the necessary isotopes ii) Specific activity of isotopes usedii) Specific activity of isotopes used
• Projects: 1) TRIUMF ISAC beam facility to pursue the1) TRIUMF ISAC beam facility to pursue the production of Rn-211 (parent of At 211)2) Sm 153 enrichment (self funded DOE)2) Sm-153 enrichment (self-funded, DOE)
11/6/2012 24TRIUMF Nuclear Medicine
Stated Goals in the 5YP
• Upgrade and transformation of infrastructurepg• National network for radiotracer development• Focused research and development of microfluidicsFocused research and development of microfluidics• Expanded cyclotron targetry for PET isotopes• Innovative techniques for mining novel radionuclides• Innovative techniques for mining novel radionuclides,
especially from the new e-linac accelerator proposed at TRIUMFat TRIUMF
• Strengthen existing partnershipsa need for facilities that meet regulatory oversight• …a need for facilities that meet regulatory oversight
11/6/2012 TRIUMF Nuclear Medicine 25
Recent TraineesName Degree Institution Date completed New Role
Tom Morley PDF TRIUMF/BCCA February‐12 MNILisa Murphy PDF UBC/TRIUMFJacqueline Cawthray PDF UBC/TRIUMFHua Yang PDF TRIUMFQing Miao PDF TRIUMFChristoph Herrmann PDF TRIUMF/UBCJames Inkster PhD TRIUMF/SFUEszter Boros PhD TRIUMF/UBC July‐11 HarvardEric Price PhD TRIUMF/UBCCaterina Ramogida PhD TRIUMF/UBCPaloma Salas PhD TRIUMF/UBCSamar Haroun MSc TRIUMF/SFU May‐11 ChromspecZara Senai MSc SFU April‐11 unknownSamantha Fregien co‐op TRIUMF/SFU August‐11 SFUKate Liu co‐op TRIUMF/UBC March‐11 McGillPhillip Danby co‐op TRIUMF/Uvic August‐12 UvicTrevor Uittenbosch co‐op TRIUMF/UBC August‐12 UBCp / gKiel Strang co‐op TRIUMF/UBC August‐11 UBCNick Zacchia co‐op RIUMF/Concord August‐11 ConcordiaBrian Badesso co‐op TRIUMF/UBC August‐12 UBCEric Himbeault co‐op TRIUMF/UBC August‐12 UBC
11/6/2012 26
p / gLaz Milovanovic co‐op TRIUMF/UBC August‐12 UBCKathleen Genge tech TRIUMF March‐12 TRIUMFSalma Jivan tech TRIUMF May‐12 UCSF
Impact
TRIUMF Nuc. Med. has obtained ~$15 million in funding as lead inst. since 2009
Grants between PPRC and TRIUMFFocus: Neurodegenerative Disease Imaging (Parkinson’s)25 year history of collaboration25 year history of collaborationTotal (past 5 years): <$14 million in peer reviewed grants (>$4M with TJR as
PI) – ~10% for TRIUMF
Grants between BCCA and TRIUMF:Focus: Functional Cancer Imagingg gTotal: $19.0 million in peer reviewed grant funds since 2008 (~25% for
TRIUMF)
Grants between other research partners and TRIUMFFocus: Novel Radiotracer Development
11/6/2012 27
Total: $600,000 (MA as PI, Nordion) $100,000 (PS as PI, GE)TRIUMF Nuclear Medicine
What’s next?
• Hiring Plan: – BAEs to drive competencies
• New cyclotron (TR24?) to replace/complement TR13y ( ) p p– Need: lower energy, higher current capabilities– Solid target infrastructureg
• Establish seamless program with partners– IP (MOUs, CRAs, etc.)( , , )– Pipeline to CCM
• NRC/TRIUMF funds are crucial for infrastructureNRC/TRIUMF funds are crucial for infrastructure upgrades, core operations, people
28TRIUMF Nuclear Medicine
What is our Critical Mass?
Positions funded using TRIUMF funds• Administrative: Head (BAE)• TR13: 3 FTEs (+1 electromechanical eng)( g)• Targetry: 4.5 FTEs (currently on soft funds)• Core Chemistry: 1 BAE, 2 FTEs (+1 chemist)*y , ( )• Project Management/Infrastructure: 1 FTEProgram Growth (BAEs):g ( )• Radiochemistry Research: +1 (hiring underway)• New Nuc. Chem./Targetry: +1 FTENew Nuc. Chem./Targetry: 1 FTE• New Applications: +0.5 FTEs (bridging position)
11/6/2012 29* Salaries paid by PPRC
Final Thoughtsg
• Beyond 2015:Beyond 2015:1) Core (Parkinson’s) program request:
• $12 2 million/5 yrs 5 FTEs• $12.2 million/5 yrs, 5 FTEs• Risk: Progress has a price:
Novelty of chemistry is diminishing– Novelty of chemistry is diminishing, – Scientific contributions will require interaction at
medical/clinical/imaging level to warrant inclusionmedical/clinical/imaging level to warrant inclusion on grants/publications.
11/6/2012 30TRIUMF Nuclear Medicine
Final Thoughtsg
• Beyond 2015:Beyond 2015:2) Research program request:
• $16 5+ million/5 yrs ($10 million for new cyclotron)• $16.5+ million/5 yrs ($10 million for new cyclotron),• 11+ FTEs
Risks Reso rce demands Critical path defined b• Risks: Resource demands; Critical path defined by peer reviewed funding
3) Detector Development • $0.9 million, 1 FTE (through TRIUMF cost centres)• Risk: Not within stated divisional focus
11/6/2012 31TRIUMF Nuclear Medicine
AcknowledgementsgTRIUMF TeamShane Basran
LeadershipNigel LockyerShane Basran
Ken BuckleyMaurice Dodd
Nigel LockyerJean-Michel PoutissouTom RuthMike AdamWade English
Linda GrahamVicky Hanemaayer
Mike AdamTim MeyerShirley ReeveHenry ChenVicky Hanemaayer
Conny Hoehr, PhDJames InksterS l Ji
Collaborators
Henry Chen
Salma JivanJulius KlugQing Miao, PhD
PPRC (J Stoessl, V Sossi, team)BCCA (F. Bénard)UBC Engineering (E Asselin)
Tom Morley, PhDChristine TakharHua Yang PhD
Edmonton (S McQuarrie, D Abrams, K Gagnon, J Wilson)Lawson (F Prato, M Kovacs)CPDC (J Valliant)Sh b k (B G i )
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Hua Yang, PhDStefan Zeisler, PhD
Sherbrooke (B Guerin)
Canada’s national laboratory for particle and nuclear physics Laboratoire national canadien pour la recherche en physique nucléaire
et en physique des particules
TRIUMF: Alberta | British Columbia | Calgary Carleton | Guelph | Manitoba | McMaster Montréal
Th k !Carleton | Guelph | Manitoba | McMaster Montréal | Northern British Columbia | Queen’s Regina | Saint Mary’s | Simon Fraser | Toronto Victoria | Winnipeg | York
Thank you!Merci!
Owned and operated as a joint venture by a consortium of Canadian universities via a contribution through the National Research Council Canada
Propriété d’un consortium d’universités canadiennes, géré en co-entreprise à partir d’une contribution administrée par le Conseil national de recherches Canada
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