Biological Systems Science Division

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Biological Systems Science Division
The Charge Given by Dr. Anna Palmisano Organize
a Workshop on New Frontiers of Science in
Radiochemistry and Instrumentation for
Radionuclide Imaging (POC Prem Srivastava)

• Goal 1 to discuss reconfiguration of the BER
  Radiochemistry and Instrumentation program to
  incorporate research relevant to DOEs missions
  in biology and environmental sciences
• Goal 2 to seek programmatic outcomes broadly
  useful and transferable to other agencies and
  industry, including nuclear medicine community.
• Goal 3 to publish the Workshop Report and make
  it available for dissemination to scientific
  community

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New Research Paradigm for Reconfiguration of
Radiochemistry Program A Driving Factor for
Organizing the Workshop New Research Paradigm
Workshop Organization
BER Biological Sciences
BER Environmental Sciences
NIH Human Health Sciences
BER Foundational Research in Radiochemistry and
Imaging Instrumentation
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Who Were the Participants? Invitation for
Participation Based on Overarching Horizontal and
Vertical Relationships of Both the Science and
the Scientists Involved
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Organization of the Workshop

• Workshop Date November 4-5, 2008
• It brought together 43 scientists from plant,
  microbial and environmental biology with
  chemists, physicists and engineers from the
  nuclear medicine research community
• Participants included from Academia, NIH, and DOE
  National Laboratories
• Charge was to jointly ascertain how
  radiochemistry and radionuclide detection
  instrumentation could be used to benefit diverse
  aspects of basic research in microbial and plant
  metabolism relevant to biofuel production and
  bioremediation, and be transferable for use in
  nuclear medicine research and applications by NIH
  and industry

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Workshop Program
Day 1 - General Session Seminars by experts
Addressing the current state of science and
future research needs Day 2 - Breakout Working
Groups Having panel discussions, and summaries
by Co-Chairs
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General Session Topics Addressing the Current
State-of-the Art and Future Research Needs

• Brain imaging from Genes to Behavior
• Nora Volkow, Director, NIDA, NIH
• Imaging Instrumentation - Tom Budinger LBNL Paul
  Vaska, BNL (2)
• Radiotracers for Imaging Applications John
  Katzenellenbogen, U.IL Urbana Jacob Hooker,
  BNL, Marit Nilsen-Hamilton, AMES, IA (3)
• Transport of Radionuclides in Biological Systems
  - Jan Schnitzer, Director, Sidney Kimmel Cancer
  Center, San Diego
• Microbial Bioremediation/Biomineralization - E.
  Kate Dadachova, Albert Einstein College of
  Medicine Patricia Sobecky, Georgia Tech (2)
• Fluorescent Probes for Visualizing Living Plant
  Cells and Plant-Associated Microbes Maureen
  Hanson, Cornell University Wolf Frommer,
  Carnegie Institution, Stanford University (2)
• Photosynthetic Biofuels Tracing Metabolic
  Pathways Tasios Melis, U.C. Berkeley

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General Session Seminars by Experts Addressing
the current state of science and future research
needs and opportunitiesBreakout Working Groups
(1- 4) Panel discussions

• Generic questions
• To what extent could your research take advantage
  of radiotracer imaging (quantitative,
  nondestructive, dynamic, living biology,
  real-time)
• What are the limitations of the various current
  techniques (depth of interaction, optical range,
  functional vs. structural, signal/background
  ratio, quantitative, and repeat-experiments
• What are the dynamic and spatial requirements for
  imaging biological processes (e.g. imaging large
  areas multiple times over the course of
  days/weeks, or molecular scale processes for
  rapid sequence imaging
• What are the ideal performance characteristics
  for new tracers and/or imaging instruments that
  could move the field forward

• General findings and new opportunities
• New more generally applicable and reliable
  methodologies to expand the range of radiotracers
  for broader use
• New radiotracer approaches for labeling of
  macromolecules and nanoparticles at high specific
  activity for PET/SPECT or multi-modality imaging
• Improvements in the radiotracer producing
  instrument design (new generator systems or
  compact and portable devices for on-site
  chemistry
• Improvements in currently available radionuclide
  imaging instruments for spatial resolution,
  efficiency, volume and geometry requirements to
  address new imaging problems in relevance to
  plants
• New imaging devices with dual-modality capability
  to address problems of resolution, object size,
  sensitivity, time scale, and operation in a wide
  range of diverse and more field-like
  environments.

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General Session Seminars by experts Addressing
the current state of science and future research
needs Breakout Working Groups (1- 4) Having
panel discussions, and summaries by Co-Chairs

• Working Group 1 Challenges and
• opportunities in radiotracer chemistry Co-
• Chairs - Dr. Jacob Hooker and Dr. John
• Katzenellenbogen
• What are the major challenges for radiolabeling
  of small molecules, oligonucleotides, peptides,
  and proteins with PET/SPECT nuclides?
• What are the capabilities and limitations for
  dual-modality labeling (pairing radioisotope
  label with MR or optical probe?)
• What are the limitations and best strategies to
  label nanoparticles which address high sp.
  activity, str. sensitivity and characterization?
• How can automation be better utilized in
  radiolabeling of molecular probes and what
  prevents more facile use of automation?

• Findings and new research opportunities
• Development of new chemical reactions to overcome
  synthetic constraints of working with
  radioisotopes at high specific activity for
  more generally applicable radiolabeling
  techniques
• Need for physical chemistry models to predict
  reactivity at the tracer mass scale for
  increased understanding of critical parameters
  and optimization of chemical reactions for
  efficient/high yield radiolabeling
• Construction of nanoparticle platforms for
  incorporation of one or more imaging agents and
  targeting moieties
• New automation technologies for readily
  adaptable, versatile and purification techniques
  (microfluidics/kits) as transformational tools
  for radiotracer synthesis for new emerging
  research areas

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General Session Seminars by experts Addressing
the current state of science and future research
needs Breakout Working Groups (1- 4) Having
panel discussions, and summaries

• Working Group 2 Challenges and
• opportunities in radionuclide and
• hybrid instrumentation development
• Co-Chairs Dr. Paul Vaska and Dr.
• William Moses
• What are the most important needs for
  Radionuclide Imaging within the DOE mission?
• What are the requirements for radionuclide
  imaging instrumentation (e.g. spatial scale for
  both resolution and field-of-view, time scale,
  radionuclide restrictions)?
• Can these requirements be met with existing
  radionuclide imaging instrumentation, and if not,
  what modifications need to be made?
• How does the information provided by radionuclide
  imaging compare to that from other modalities and
  what are the potential advantages of
  multi-modality imaging (e.g. interrogating
  several biochemical processes at the same time)?

• Findings and new Research opportunities
• Explore new scanner geometries to match the
  diversity of new uses and size scales - existing
  PET/SPECT devices need to be improved for
  different geometries and field of view ranging
  from 100 µm spatial resolution to m3 volumes for
  plant and microbial research
• Develop higher resolution-PET detector systems
  resulting in a dramatic improvement in spatial
  temporal resolution, and sensitivity current
  systems need to be improved by an order of
  magnitude approaching the fundamental limits of
  spatial resolution for sub-mm scale biological
  imaging
• Explore benefits of dual-modality imaging -
  adding complementary imaging would enhance the
  applications of radiotracer techniques to studies
  in plants and microbes
• Develop imaging devices capable of operating in
  diverse environments for functioning in a
  laboratory, greenhouse or field environment (as
  opposed to a hospital)

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Breakout Working Groups (1- 4) Having panel
discussions, and summaries

• Working Group 3 Radioisotope
• methodologies for probing plants,
• microbes and the environment
• CoChairs Marit Nilsen-Hamilton and
• Silvia Jurison
• What aspects of plants and microbes research
  would most benefit from new, nondestructive,
  functional, real-time radionuclide imaging
• Working Group 4 Identification of new
• technologies developed for plant and
• environmental biology that will be
• applicable to stimulating new advances in
• nuclear medicine CoChairs Robert Mach,
• Tom Budinger and Henry VanBrocklin
• What biological/biochemical processes of
  relevance are shared across species for which
  radiotracers and instruments with special
  characteristics could be broadly applicable
  (nuclear medicine)

• Working Group 3 4 (Combined findings
• and new opportunities)
• New radiochemistry and instrument methodologies
  for biology and environment- with applications to
  nuclear medicine
• Low energy (3He or a tandem cascade
  proton/deuteron) accelerator having a reduced
  power demand, low neutron flux, and small
  footprint
• New detector systems 1) with high spatial
  resolution and high sensitivity and 2) that
  directly measure charged ions (b, b-, Auger
  electrons) needed for plant and microbial
  imaging, will also be beneficial for nuclear
  medicine research and applications
• Need of radiotracer techniques to study carbon
  flow dynamics with PET (C-11) in combination
  with14C MS and hyperpolarized 13C NMRS

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Summary

• The Workshop Report provides an analysis of the
  current state of radiotracer chemistry,
  radioanalytical methodology, and imaging
  instrumentation and then presents a series of new
  opportunities for DOE developments in areas that
  could provide major benefits to fundamental
  research in alternative energy production and in
  the environmental sciences.
• It was recognized, however, that this effort was
  only a beginning. With a clearer recognition of
  the capabilities that basic radiochemistry and
  radionuclide imaging instrumentation technologies
  can provide to biologists and environmental
  scientists and a better understanding of the
  problems being tackled in plant biology by the
  chemists, physicists, and engineers, this merger
  of talent has great potential for advancing
  current DOE missions.

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ACKNOWLEDGMENTS

• This report is based on the workshop and was
  developed from the interaction of the workshop
  participants. They were divided into working
  groups whose leadership authored the contents.
• Authors are
• Thomas Budinger, Co-Editor
• John Katzenellenbogen, Co-Editor
• Jacob Hooker
• Silvia Jurisson
• Robert Mach
• William Moses
• Marit Nilsen-Hamilton
• Henry VanBrocklin
• Paul Vaska
• Review of the Final Report
• The writing team, as well as Jill Banfield,
  Maureen Hanson, Patricia Sobecky and Ming Tien

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THANK YOU

• The Whole gt S partsi

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Figure 5. Temporal and spatial scales involved
in photosynthesis.1
1 Original concept from Osmond CB and Chow, WS.
1988. Aust. J. Plant Physiol. 151-9. Modified
after Kiser, et al. 2008. HFSP Journal 2189-204.
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Figure 7. Major pathways of photosynthesis and
plant metabolism1
1 Created by Scott Taylor, Lawrence Berkeley
National Laboratory, and Tasios Melis,
University of California, Berkeley, Nov. 2008.
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For on-site applications requiring radiotracer
and associated chemistry and imaging in the field
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The Role of Microbial Phosphatases on Uranium
Mobility in the Subsurface (Patricia Sobecky and
Co-Workers)
Blue Rahnella Green Bacillus
Non-specific Acid Phosphohydrolase (NSAP)mediated
release of phosphate from organophosphates
immobilizes toxic metals (Martinez et al. 2007
Beazley et al. 2007)
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