nuclear medicine - triumf nucmed-ppac1.pdf · nuclear medicine: vision and goals ppac, nov. 1st,...

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


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


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


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





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


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


, 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

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

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)


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.


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


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 )

32

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

nuclear medicine - triumf nucmed-ppac1.pdf · nuclear medicine: vision and goals ppac, nov. 1st,...

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