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
Paul Schaffer  Head, Nuclear Medicine  TRIUMF
Assistant Professor Radiology  University of British Columbia
Adjunct Professor Chemistry  Simon Fraser University
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Accelerating Science for Canada
Un accélérateur de la démarche scientifique canadienne
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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Outline
• Context of Nuclear Medicine at TRIUMF
• Accomplishments 2008-2013
• Future plans 2015-2020
• IAMI – Institute for Accelerator-Based Medical Isotopes
• Program growth around core competencies:
• Accelerator Targetry
• Nuclear Chemistry
• Radiopharmaceutical Chemistry
• Scenarios
13 Nov 2013
Nuclear Medicine
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TRIUMF’s Research Program
13 Nov 2013
3
Vision Statement
• TRIUMF Nuclear Medicine will emerge as a Centre
for Excellence in all aspects of medical isotope
research
• To be a regional enabler for academic and privatesector research involving isotopes and isotope
production technology
• Growth with focus on three facets of program:
• Training: attract and train HQP
• Innovation: address unmet technological needs
through innovation
• Quality: deliver and/or enable leading edge
science
11/12/2013
TRIUMF Nuclear Medicine
4
Context
Q 1: What is the role of TRIUMF in supporting Canadian and international
scientists and students (in Nuclear Medicine Research)?
13 Nov 2013
Nuclear Medicine
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TRIUMF Nuclear Medicine Today
Core Competency: Accelerator Targetry
• Innovating new target solutions: High-power, versatility
• Driving the new medical isotope paradigm
• Looking forward: ISAC-ISOL
Core Competency: Nuclear Chemistry/Isotope
Production
• Legacy Program: 18F/11C production
• Radiometals, Actinides
Core Competency: Radiochemistry
• PPRC-Neurology: New directions
• BCCA-Oncology
• New ideas/Novel Applications
6
Scale of TRIUMF’s Involvement
Research Scientists
Support Staff
NRC funded
Grant Funded (UBC)
Grant Funded (TRIUMF)
Total FTE
Competency
Isot. Prod./
Targetry
Radiochem
Nucl. Chem
1
1
2
4.5
2
2
3
2
2
5.5
5.5
3
4
Target Effort: Seconded to Nat. Resources Canada – ITAP
Isotope Production: Scientist = shared indiv. with Accel. Div.
- 2 FTE focus on TR13 Ops, support other efforts
Radiochemistry Effort:
- 3 FTE focus on UBC Imaging Program, tracer production
- 1 FTE pursuing additional interests
13 Nov 2013
Nuclear Medicine
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Nuclear Medicine - Outputs
Creating Leaders (HQP) 2008 – 2013
highschool
Graduations
5
undergrad
18
MSc
1
PhD
3
PDF
5
EIT*
2
*EIT = Engineers in Training
Advancing Knowledge
(2008 – 2013):
2013 YTD: 12 published,
* 3 accepted
*
8
TRIUMF’s Role in the Canadian
and Int’l Community
Deep Expertise + Focus on Competencies = Results
Natural Resources Canada (NRCan):
Focus: Alternative Production of 99mTc
TRIUMF leads 4-institution effort across Canada, Int’l attention
Pacific Parkinson’s Research Centre (PPRC) and TRIUMF:
Focus: Neurodegenerative Disease Imaging (Parkinson’s) - 25 year partnership
2008-2013: $14.5 M in peer reviewed grants (>$4M with TJR as PI)
Sossi
~10% for TRIUMF
BC Cancer Agency (BCCA) and TRIUMF:
Focus: Functional Cancer Imaging – New capabilities / Program growth
2008-2013: $18.2 M in peer reviewed grants
Note: NRCan-NISP ($6M) and ITAP ($7M) led by TRIUMF
Other research partners (UBC, SFU, Nordion): $0.86 M
Leveraging Collaboration:
NRC funds since 2008: ~$2.3 M
(ratio of ~10:1 in additional grant funding) 2.25:1 direct to TRIUMF
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TRIUMF’s Role in the Canadian
and Int’l Community
1600
1400
Runs by experiment per month
TR13 runs per year by institution
100
BCCA
UBC
90
80
1200
70
1000
800
600
LS101
LS99
LS98
LS97
60
50
40
LS94
LS93
LS92
LS91
30
400
20
200
10
0
0
LS89
LS56
LS8
LS4
LS3
LS0
Current Demands:
Hoehr
97.5% beam delivery (659 runs)
PPRC/UBC Imaging Program: 80.3% of runs; BCCA:1.8%
User base includes: UBC Chemistry, Oceanography, Botany
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and SFU Chemistry
Highlights 2008-2013
Q 2: To what extent are TRIUMF’s research activities, on a national and
international scale, considered leading edge?
Q 3: To what extent has key knowledge been generated as a result of
TRIUMF’s activities?
Q 4: To what extent has TRIUMF elevated Canada’s reputation and
international leadership in physics?
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Nuclear Medicine
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Infrastructure for Positron Emitting
Radiopharmaceutical (PERs) Production
13 Nov 2013
Nuclear Medicine
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Pneumatic Pipeline: Radiotracer Transfer
New transfer line
to CCM
imaging facility
TRIUMF Nuclear Medicine
Centre for Comparative
Medicine (CCM)
CCM: BC Preclinical Research Consortium
- Collaborative hub
-
V Sossi (Science), P Schaffer (TRIUMF)
and U Hafeli (Pharm)
- Enabler: BC Life Sciences
Community
Transfer
line
to CCM
imaging
facility
VECTor PET/SPECT/CT:
Status: Delivered and operational
- TRIUMF- CCM transfer line needed
- installation delayed
- Imaging studies have commenced
Transition to GMP / New Tracers
Process move from custom ASU to GE ASU:
 11CH4 to11CO2
 11C-MRB: norepinephrine transp.
 11C-DASB: serotonin transp.
 11C-PBR28: cerebral inflammation
 11C-Yohimbine: adrenergic receptor
11C-Raclopride, 11C-PMP, 11C-DTBZ
 11C-FLB: extrastriatal dopamine
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Additional Infrastructure
Yang
Add’l Radiochem Research
Radiochemistry Lab Upgrade
Offices (26)
Nuclear Medicine:
Accelerator Targetry
• Advancing Isotopes for Science and Medicine
• Harnessing Particles and Beams to Drive
Discovery and Innovation
• Direct production of 99mTc via 100Mo(p,2n)
13 Nov 2013
Nuclear Medicine
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Direct Production of 99mTc via 100Mo(p,2n)
To demonstrate existing
cyclotron network….
100Mo
Target
100Mo
Cyclotron
Modifications
Recycle
Buckley
100Mo(p,2n)99mTc
Irradiation
Parameters
Regulatory
Purification
of 99mTcO4-
…can produce
commercial quantities
of 99mTc
Goal: Help formulate Government of Canada policy
on 99Mo/99mTc medical isotope production
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Direct Production of 99mTc via 100Mo(p,2n)
Tc in BC: (TRIUMF + BCCA):
• Reproducible production >10Ci (600 patient doses/day)
• Operating at 230 A on target, 6 hrs (Goal: 300 A, 6 hrs)
• Meet greater Vancouver area demands from one machine
Tc in Ontario: (Centre for Probe Development and
Commercialization and Lawson Health Research Inst.):
• Operating at 100A, 1 hr (Goal: 130A, 6 hrs)
• Regulatory efforts set to begin NDS
paperwork process
• Process continues to be refined
Since 2010: >50 Knowledge products
• 3+ patents
• 100’s of media ‘hits’
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Direct Production of 99mTc via 100Mo(p,2n)
Transfer
Drive
Purification
Module
Receive
and
Dissolve
13 Nov 2013
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Nuclear Medicine:
Nucl. Chem./ Isotope Production
• Advancing Isotopes for Science and Medicine
• Harnessing Particles and Beams to Drive Discovery and
Innovation
• 18F/11C production
• Radiometals from liquid targets
13 Nov 2013
Nuclear Medicine
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Radiometals from Salt Targets
Objectives:
- Enable production of expanded repertoire of radiometallic isotopes
at TRIUMF with minimal infrastructure changes
- Enable isotope-biomolecule pairing studies for in vivo optimization
Completed: 94mTc from natMo, 44Sc from natCa
Current effort: 89Zr from natY, 68Ga from natZn and 86Y
from Sr
Accessible Technology:
- Production with 5 µA, 13 MeV, 60 min
- Yields: sufficient for radiochemistry, pre-clinical
studies
Strong training component
-
Oehlke
4 undergrad, 2 PhD, 1 PDF
Appl. Radiat. Isotope 2012, 70, 2308-12
Nucl. Med. Biol. 2013, accepted, in press
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Hoehr
ISOL 211Rn/211At & 209At
209At
99mTc
18F
Crawford
Objectives:
Initiate TRIUMF Targeted Alpha Therapy Isotope program
Est. 211Rn/211At generator
Production via ISOL/UCx target
Use 209At to image, est. biodist.
Use unique infrastructure, training opportunities
Springboard into collaborative interests:
SOREQ, U. Strathclyde (225Ac/ 213Bi, 211/209At)
Thanks to: TRIUMF RPG, ISAC, PHAS, CCM
ISAC
Other Efforts
Genome BC: Antisense PET
Goal: Modular synthesis, Isotope/vector pairing studies
Thanks to: BCCA (imaging), Nordion (Ga-67), TR13 (Sc-44)
CPP
PNA
HIV Tat
peptide
Anti-HER2
Signal
Generator
F-18 / optical
Sc-44, Zr-89, Ga-67
Ir-192 (with Corina Andreiou, Tim Storr, SFU)
Goal: Demonstrate production and radio-organometallic
chemistry to novel Ir-192 complexes
Thanks to: S. Zeisler, V. Hanemaayer for guidance in natOs target dev.
*** see posters
Miao
Langille
Nuclear Medicine
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Nuclear Medicine:
Radiopharmaceutical Chemistry
• Advancing Isotopes for Science and Medicine
•
•
•
•
Core Program – new tracers (slide 15)
Radiometals / pairing studies (previous slide)
Novel chelates
Oxidative Stress – 18FASu
13 Nov 2013
Nuclear Medicine
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Applications: Oxidative Stress
(xC-) Imaging
Goal: Establish new tracer to monitor
amino acid transport
Aim 1: establish tracer specificity
Aim 2: establish 18FASu uptake  transporter
Aim 3: demonstrate clinical utility of 18FASu
18FASu vs 18FDG uptake in SKOV3 tumors
35
30
25
20
FASu
15
FDG
10
5
0
‐5
%ID/g
tumor:blood
tumor:muscle
Hua Yang: 2nd Place in 2013 SNMMI Young Professionals
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Radiochemistry: Acyclic Chelates
for Imaging with Radiometals
Goal: to enable radiometal incorporation onto large mol.
wt. radiotracers
Adam
• Expanding the dedpa/octapa scaffold for use with other
radiometals (111In, 90Y, 44Sc, 225Ac, 89Zr, 177Lu)
Eric Price: Winner of 2013 SNMMI Berson-Yallow Award
27
Nuclear Medicine:
Proton Therapy
• Harnessing Particles and Beams to Drive Discovery and
Innovation
• Monte Carlo simulations to improve facility and
methodology
• PET after PT for dose assessment
Hoehr
13 Nov 2013
Nuclear Medicine
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Nuclear Medicine
2015-2020
Q 9: Are the proposed activities included in TRIUMF’s 5-year plan appropriate
and consistent with the needs and ambitions of the physics community, both in
Canada and internationally? Will the plan elevate Canada’s reputation and
international leadership in nuclear medicine, nuclear physics, materials
science, particle physics and accelerators research?
Q 10: Do the requested resources and the laboratory’s capabilities give
reasonable confidence that the activities of the 5-year plan can be carried out
to achieve the stated outcomes?
13 Nov 2013
Nuclear Medicine
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Nuclear Medicine Goals: 2015-2020
2015-2020
2010-2015
2005-2010
Pre-2005
- IAMI
- New Cyclotron
-ISAC/ARIEL
- Exploit Facility Upgrades
- Succession begins
- Nuc. Med. Growth: C Hoehr BAE
- Nuclear Medicine becomes division
- New program with BCCA
- Broadened partnership with UBC Imaging
Program
- Nuc. Med Growth – P. Schaffer arrival
- Facilities upgrade (GMP, MHESA)
- Est. deep
expertise in:
Targetry
Nucl. Chem.
Radiopharm. Applications (PPRC)
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Nuclear Medicine Goals: 2015-2020
• Targetry
• Commercialize / Product 99mTc
• New target designs
• Nuclear Chemistry
• ISAC/ARIEL programs
• Alpha isotope program development, build capabilities
• Prepare for ARIEL isotope production program
• Radiochemistry: PPRC/UBC Imaging Program
• New thrusts as defined by PPRC
• Full regulatory compliance
• Novel Applications
• Collaborative: Technology, new isotopes, imaging
• Internal: Oxidative stress imaging, Chelates
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Institute for Accelerator-Based
Medical Isotopes (IAMI)
Goal: Capital and Operational Upgrade for Nuc. Med. Research
New Research
- Therapeutic isotopes
PPRC/GMP program
- Meet demand
- Enable new interests
TR24
Commercial program
- 99mTc, 18F
- Vancouver supply
Research program
- Added capacity, CCM
TR13
Research program
- Target/Nucl. Chem
- Radiochemistry
- Applications
Training program
- CREATE (Kruecken)
- Courses taught
Nuclear Medicine
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Nuclear Medicine Goals: 2015-2020
• IAMI
• Represents major Nuc. Med. Initiative for next 5YP
• Critical enabler for all things involving medical isotopes
• Current stakeholders: PPRC/UBC Imaging; BCCA; Nordion;
UBC Physics/Chemistry/Oceanography, ACSI, SFU Chemistry
Goals:
• Expanded user base (private and academic)
• Leverage CCM/Preclinical Research Consortium infrastructure
• Expanded Research Capacity
• Focus remains on competencies
• Core support for Cyclotron Operations, GMP
Radiopharmaceutical production, QA
• Training
13 Nov 2013
Nuclear Medicine
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Budget Scenarios
Scenario A – Exploit opportunities for enhanced impact
• Tc-99m: Prepare Canada for Chalk River reactor shutdown (2016)
• IAMI:
• Pursue R&D that defines the current state-of-the-art in acceleratorbased isotope production
• Foster Canadian excellence by bringing together researchers with
related interests and needs
• Provide expertise and facilities to enable their research
• Nurture research translation
• PPRC: Formal PERs regulatory program comes online
Scenario B – Maintain core, avoid growth & increase risk
• Retract to focus on existing, focused program. Hold status quo
• Emphasis will be on existing program: PPRC, CCM
• Reduced IAMI scope
13 Nov 2013
Nuclear Medicine
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Scenario C - Downward spiral
Scenario C – Reduced resources, restrict program
• Nuclear Medicine at TRIUMF becomes irrelevant
• Concentrate research on core Operations (TR13, PPRC)
• Increased risk to PPRC Parkinson’s program (regulatory)
• Increased chance of major failure(s) leading to extended
downtime
• Reduce support for staff and operating activities with targeted,
deep cuts
• Reduced competitiveness: Research and Commercial
• Increased scientific backlog
• Loss of HQP (recall seconded FTEs: NRCan effort), Users
• Canada would lose a unique resource and skillset to advance an
accelerator-based (non-reactor) isotope production paradigm 35
Scenarios: Overview
2010-15
A
B
C
$ 2.3 M
$2.5 M
$1.8 M
$1.2 M
N/A
$ 1.5 M
$ 0.5 M
$
Contribution Agreements
$ 4.7 M
$ 5.5 M
Grants (NSERC, CIHR, GBC)
$1.4 M
Nuc. Med. Operating Budget
Core Ops (UBC)
Infrastructure
Research/Comern Support
IAMI
-
Operations
Regulatory Compliance/QA
Research Capacity
Other Support:
13 Nov 2013
Nuclear Medicine
?
?
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Summary
• TRIUMF Nuclear Medicine has capitalized on its core
competencies to:
• Lead and innovate with new partnerships: 99mTc
• Evolve program to explore new initiatives: BCCA
• Continue to enable our long-standing partners: PPRC
• With requested funding (Scenario A):
• TRIUMF will establish the IAMI as a regional enabler with
national and international reach
• Allow for increased focus on emerging regulatory
requirements for PERs
• Provide a means to create social
and economic growth through
innovation and commercialization
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Canada’s national laboratory for particle and nuclear physics
Laboratoire national canadien pour la recherche en physique nucléaire
et en physique des particules
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
TRIUMF: Alberta | British Columbia |
Calgary | Carleton | Guelph | Manitoba |
McGill | McMaster | Montréal | Northern
British Columbia | Queen’s | Regina |
Saint Mary’s | Simon Fraser | Toronto |
Victoria | Winnipeg | York