November 21, 2014
Dr. Lawrence S. Cardman
Chairman, Isotopes Subcommittee
Nuclear Science Advisory Committee
The Society of Nuclear Medicine and Molecular Imaging (SNMMI) would like to thank the Nuclear
Science Advisory Committee (NSAC) for the opportunity to submit input comments as you continue your
deliberations. As you know, SNMMI is a nonprofit scientific and professional organization that promotes
the science, technology and practical application of nuclear medicine and molecular imaging. SNMMI
strives to be a leader in unifying, advancing and optimizing molecular imaging, with the ultimate goal of
improving human health. With 18,000 members worldwide, SNMMI represents nuclear and molecular
imaging professionals, all of whom are committed to the advancement of the field.
SNMMI appreciates the chance to summarize our thoughts and ideas regarding the radioisotope charge
to the NSAC. Nuclear medicine professionals use several isotopes that are supplied by the Department
of Energy (DOE) Isotope Program (DOEIP), in addition to commercial and university sources. These
isotopes include:
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Actinium-225 (Ac-225)
Astatine-211 (At-211)
Bromine-76 (Br-76)
Copper-64 (Cu-64) – Not commercially available
Copper-67 (Cu-67)
Holmium-166 (Ho-166)
Iodine-124 (I-124) – Now commercially available
Lead-203 (Pb-203)
Lead-212 (Pb-212)
Lutetium-177 (Lu-177)
Manganese-52 (Mn-52)
Radium-223 (Ra-223)
Radium-224 (Ra-224)
Rhenium-188 (Re-188)
Strontium (Sr-82)
Strontium-90 (Sr-90)
Thorium-227 (Th-227)
Tungsten-188 (W-188)
Yttrium-86 (Y-86)
Zinc-69m (Zn-69m)
Zirconium-89 (Zr-89) – Now commercially available
Unfortunately, the availability of these isotopes, particularly Sr-82, Ac-225, and Lu-177, varies greatly.
Sr-82 is currently in short supply and the demand exceeds the supply available from global sources.
Ac-225 is also in short supply. Finally, production of Lu-177 by direct neutron capture is outdated given
the metastable long-lived isotope. As a result, it is not suitable for human use.
The DOE Isotopes Program has been helpful and supportive through the production of isotopes, both
radioactive and enriched, that are needed for the practice of nuclear medicine. In some cases, the
Department of Energy is the sole source of those isotopes. However, SNMMI believes that there are
some areas where the DOEIP could better support our needs. Isotope production is often not the driving
force in operational decisions. As a result, costs are not necessarily accrued based on the incremental
nature of isotope production as is the case with the High Flux Isotope Reactor (HFIR) isotope production,
where reactor operational costs are included despite the fact that it would still operate in the absence of
isotope production.
There also needs to be consideration for the availability of enriched stable isotopes. They are used to
produce radionuclides in both reactors and accelerators. In the case of radioisotopes that have a large
clinical use, the continuing need for the enriched isotopes for targets is critical to sustaining the
availability of those radiopharmaceuticals. An example of a growing need is the availability of Nickel-64
for the production of Copper-64. These isotopes have to be produced in a manner that is economical
and sustainable. While there has been research and development done on the topic at ORNL, this work
will not supply large quantities of isotopes required for clinically useful radioisotope production. There is
a need for efforts similar to the international outreach for accelerator production to maintain supplies of
enriched stable isotopes.
As you know, the DOEIP has developed a process for the consideration of transition of isotopes from
DOE production to commercial production. There has only been one transition made during the
program's residence in Nuclear Physics. This transition ceded the production for sources to the
commercial entity, while keeping generator isotope production at the DOE. This was in response to a
comment from the community regarding the danger of a monopoly producer also being a competitor in
the generator space.
SNMMI has identified important goals we would like the DOEIP to review and consider as it works to
develop its long range plan. SNMMI asks that the DOEIP better assess the needs of the market when
making decisions regarding the expenditure of research funds. In some instances, market forces may
have been neglected in favor of purely technical reviews which ignore the presence of commercial
producers and the lack of any substantive demand by the nuclear medicine community. If market forces
are also considered in production decisions, it would maximize the efficient use of limited funds toward
the production of radioisotopes that are needed. Additionally, the DOEIP must develop a clear policy for
public/private partnerships in isotope production. Specifically, the need for a partnership between the
DOEIP and commercial entities that are developing high current, high energy accelerators in the absence
of a DOE program to follow the NSAC subcommittee recommendations. SNMMI also believes that the
DOEIP should accelerate the incorporation of university-based resources into the program, since existing
national lab-based facilities are not optimal for production of smaller quantities of radioisotopes from
reactors or accelerators. There is a need for a clear commitment to funding research at universities
where students and post-docs will receive training in topics related to isotope production including
nuclear chemistry, radiochemistry and separation chemistry. Included therein is a commitment to
support the Nuclear Chemistry summer school, which has historically attracted a significant number of
students into the field. Finally, we believe there must be a multiyear commitment to producing isotopes
for nuclear medicine research that reflects the reality of National Institutes of Health (NIH) funded
research. A minimum commitment of five years is required to reflect the application process and the
subsequent performance period.
There are several isotope-related research projects SNMMI would like to see included in the DOEIP’s
evolving list of compelling opportunities for the next decade. SNMMI believes that the DOEIP must:
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Create a program to develop the separation of Thorium-229 (Th-229) from existing Uranium-233
(U-233) inventory to expand the production of Ac-225 that is suitable for direct human use.
Develop a crash program to utilize metal targets for Sr-82 production in order to increase
production with existing facilities.
Focus on indirect production of Lu-177 that eliminates Lu-177m from the product. The
metastable isotope presents radiation dose issues for the patient and radioactive waste disposal
issues for the radiopharmacy.
Give precedence to university-based research proposals, including those in partnership with
DOE labs, to maximize the impact of those funds given the lower costs at universities and to
increase the training of students at the undergraduate and graduate level.
Work within DOE offices to establish funding for the accelerator research program now
managed by High Energy Physics (HEP) that also includes research on lower energy accelerators
that are widely used for the production of PET radioisotopes. There is currently no mandate for
supporting research for this part of the program.
Nuclear medicine cannot function without radionuclides. In particular, this list represents some of the
most important needs for nuclear medicine in both clinical research and clinical practice. There are
nonradioactive biomarkers available, but none come close to providing the physiologic information that
radioactive biomarkers can provide in patients. These radioisotopes are needed for the development of
new diagnostic and therapeutic radiopharmaceuticals, such as Ga-68 DOTATATE and Lu-177 DOTATATE.
For that reason, SNMMI strongly advocates for a partnership between the NIH and DOEIP that identifies
radionuclides of interest to the fields of nuclear medicine, radiation oncology, cardiology and neurology.
This partnership would also generate a direct funded program from which the NIH funds the production
of radioisotopes to their grantees. This would increase efficiency by avoiding paying the overhead at the
research institution. It would also generate a market based list of isotopes produced for NIH by DOE.
SNMMI remains grateful for the opportunity to submit input comments on the Nuclear Science Advisory
Committee’s long range plan. As always, SNMMI is ready to discuss any of its comments with the NSAC.
In this regard, please contact Susan Bunning, Director of Health Policy and Regulatory Affairs, by email at
[email protected] or by phone at 703-326-1182.
Respectfully submitted,
Virginia Pappas, CAE
Chief Executive Officer