JM POUTISSOUACOT

13 March 2009

Nuclear Medicine Division

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 CANADIEN POUR 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

• The Science we do

• Our people power

• Our infrastructure

• Our goals

• A canadian vision

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,..)

MolecularImaging

RadionuclideResearch

Radiotracers

Areas of Research where TRIUMF Excels

Technologies/Detectors/computing

Radiochemistry Accelerators

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

Science with academia: UBC

• Pacific Parkinson Research Centre

• UBC Psychiatry

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.

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.

4004 Wesbrook Mall Vancouver, B.C. Canada V6T 2A3

Tel: 604 222-1047 Fax: 604 222-1074

www.triumf.ca

Support- >$4.4M/year

Pacific Parkinson’s Research Institute

BCKDFPARF

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.

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.

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

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

New MHESA Radio-chem lab

The Team

Nuclear Medicine Division

J.M. Poutissou (Interim)

Deputy M. Adam

Radio ChemistryM. Adam

Production

S. Jivan

R/D

M. Adam

- New TBA- J. Lu- J. Inkster- Students- Students

UBC BCCA

- J. Greene

- C. Takhar

- V. Barreras

Cyclotron Operations

C. Hoehr

- W. English

- L. Graham

- V. Barreras (BCCA)

CFI

T. Ruth

Camera Support

- [G. Sheffer] (Detector Group)

Targetry/Methodolgy

New Lab/GMP

K. Buckley

-M. Dodd

-Post Doc (TBA)

- [TBA]

- [M. Vuckovic]

- [Y. Rozen]

Accelerator Division

Operations

R. RueggSafety/Training/Documentation

TBA

MDS Nordion

R/D

- D. Wester

- C. Ferreira

LSPEC

Nuclear Medicine Division

PET director (on leave from Sept 01/08 to Aug 31/09) PPRC director AJ StoesslV Sossi

PET acting director AJ Stoessl

Katie DinelleLab ManagementStaff/Student supervisionScanner scheduling

Stephan BlinderScanner sofware MaintenanceStudent SupervisionPhysics Experiments

Carolyn EnglishPET TechnologistScanner scheduling

Caroline WilliamsPET Technologist

Nasim VafaiSoftware Management

Salma JivanChemistry developmentScanner scheduling

Jennifer GreenRoutine Chemistry/Scheduling

Ryan ThomsonSystem Administrator

Siobhan McCormickSmall animal imaging and human image analysis

Rick KornelsenSmall animal imaging, animal handling and small animal image analysis

Jian-Ming LuPrecursor Development

Henry NgoCo-op student

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 PsychiatryA Young (UBC- Psychiatry

Individual project related fellows, coordinators,Postdocs and students

Christine TakharRoutineChemistry

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

Work planShort 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

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

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

Syringe PumpsChip in

Chip Holder

Hot plate

Collection Vial

CH3I/CH3CN solution

Precursor Solution

Monitor and VCR

Syringe Pumps

Microscope

CCD Camera

Chip

Experimental Setup

S. Haroun, SFU

11C-Raclopride – fluidic approach

No detectableMass peak!

Hot offthe press 11C-raclopride

11CH3I

11C-Raclopride – Traditional Method

Personnel requirements

• Search for Head of Division

• Add Radio-chemist

• Post Doctoral fellows

• Students

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.

TJ Ruth

09 May 2008

National CFI Proposalon Radiotracer Development

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 CANADIEN POUR 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

Mechanisms for Inclusion• National CFI – Natural vehicle for funding

• CAMINET – Driver for the future

CanadianCollaborators

CFI

Industry

CECRs

CAMINETInstitutions

The 14 Partnering Institutions

• 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

Active Cyclotron Based Programs Establishing Cyclotron Programs

Terry Fox Research Institute

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.

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

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