NSAC Isotopes Subcommittee Meeting

January 20, 2015

Erin Grady, MD

Society of Nuclear Medicine and Molecular Imaging

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SNMMI

• Represents professionals in the field of nuclear medicine

– Physicians

– Technologists

– Scientists

– Pharmacists

• 18,000 members

• Members from the United States and 79 foreign countries

• Publishes three journals and conducts two national meetings each year

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Nuclear Medicine in the United States

• Vital part of diagnostic and therapeutic management of patients

• We conduct 18 million imaging studies per year

– Tc-99m is used in 80 % of these studies

– Nuclear cardiology represents 50 %

– Nuclear oncology represents 25 %

– Other imaging of brain, endocrine system, lungs, GI & GU tract, bones, infection...and the list goes on

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Availability of Isotopes

• The availability of isotopes is crucial to the development of new targeted molecular imaging and therapeutic agents.– Targeted agents help improve the differential diagnosis, prognosis,

planning and monitoring of treatment

– Targeted agents allow physicians to tailor therapy for patients based on their specific molecular profile

– Targeted agents allow for a noninvasive imaging assessment, which can evaluate the treatment response prior to changes in tumor size determined by CT or MRI, as these modalities are based on slower to develop anatomical changes

– Targeted agents produce images based on physiologic changes

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Comments on NSAC’s Isotope Subcommittee Charge

• Last year, the Nuclear Science Advisory Committee (NSAC) provided an opportunity to comment as they deliberated on their Isotope Subcommittee's radioisotope charge.

• SNMMI provided comments on several issues, including:– Availability of isotopes used by nuclear medicine professionals

– How the Department of Energy Isotope Program (DOEIP) could better support our needs

– Consideration for the availability of enriched stable isotopes

– Suggestions for the DOE Isotope Program (DOEIP) to consider as it works towards developing a long-range plan

– Isotope-related research projects

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Isotopes Used By Nuclear Medicine Professionals

• Nuclear medicine professionals use several isotopes that are supplied by the DOEIP, in addition to commercial and university sources. These isotopes include:

─ Actinium-225 (Ac-225)

─ Astatine-211 (At-211)

─ Bromine-76 (Br-76)

─ Copper-64 (Cu-64)*

─ Copper-67 (Cu-67)

─ Holmium-166 (Ho-166)

─ Iodine-124 (I-124)

─ Lead-203 (Pb-203)

─ Lead-212 (Pb-212)

─ Lutetium-177 (Lu-177)

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─ 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)

*Not Commercially Available

Clinical Vignette – Mr. A

• 81 yo male with metastatic prostate cancer to the bones

– Reports to 1st treatment with severe pain, uses walker

– Reports to 2nd treatment no longer with the walker, pain improving, happier, fewer pain medications

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Clinical Vignette – Mr. B

• 67 yo male with metastatic prostate cancer to the bones

– Reports to 1st treatment with severe pain, unable to lift

– Reports to 2nd treatment now reporting that pain has improved, now able to lift boxes…even unloaded an entire truck with donated clothes for the charity he and his son run.

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Not only is there

improvement in

symptoms, but

also more

importantly a

SURVIVAL

BENEFIT

Myocardial perfusion studies with Rb-82 chloride

• 55 year-old male with equivocal chest pain

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Availability of Radioisotopes

• The availability of our radioisotopes, 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 supplies must be expanded from existing U-233 to provide material that can be used directly in clinical trials.

– Production of Lu-177 by direct neutron capture is outdated, given the metastable long-lived isotope, and it is not suitable for human use.

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Department of Energy Isotope Program (DOEIP)

• The DOEIP 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 DOE is the sole source of those isotopes.

• While supportive, there are some areas where they 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.

• For example, with the High Flux Isotope Reactor (HFIR) isotope production, the reactor’s operational costs are included despite the fact that it would still operate in the absence of isotope production.

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Enriched Stable Isotopes

• There must be consideration for the availability of enriched stable isotopes. – Enriched stable isotope are used to produce radionuclides in reactors and

accelerators.

• For radioisotopes with a large clinical use, the continuing need for enriched isotopes for targets is critical to sustaining their availability. – The availability of Nickel-64 for the production of Copper-64 is an example of

this growing need.

– These isotopes have to be produced in a manner that is economical and sustainable.

– While there has been research and development done on this topic at Oak Ridge National Laboratory, 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 the supply of enriched stable isotopes. 13

Important Goals for the DOEIP

• SNMMI has identified important goals we would like the DOEIP to review and consider as it works to develop its long-range plan. – Better assess the needs of the market when spending research funds.

– Develop a clear policy for public/private partnerships in isotope production.

– Accelerate the incorporation of university-based resources into the program.

– Make a multiyear commitment to producing isotopes for nuclear medicine research that reflects the reality of NIH funded research.

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Important Goals for the DOEIP

• Better assess the needs of the market when spending research funds. – Market forces may have been neglected in favor of purely technical

reviews that ignore the presence of commercial producers.

– Consideration of market forces in production decisions would maximize the efficient use of limited funds toward the production of radioisotopes.

• Develop a clear policy for public/private partnerships in isotope production. – 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.

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Important Goals for the DOEIP

• Accelerate the incorporation of university-based resources into the program.– Existing national lab-based facilities are not optimal for production of

smaller quantities of radioisotopes from reactors or accelerators. – A commitment to funding research at universities where students and

post-docs will receive training in topics related to isotope production.

• A multi-year commitment to producing isotopes for nuclear medicine research that reflects the reality NIH funded research.– A minimum commitment of five years is required to reflect the

application process and the subsequent performance period.

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Isotope-Related Research Projects

• There are several isotope-related research projects SNMMI members have expressed interest in and would like to see included in the DOEIP’s evolving list of compelling opportunities for the next decade – Investigate alternate routes for production of Ac-225 for human use to expand

availability of this important isotope

– Develop methods to increase production of Sr-82 to expand current capacity

– Expand the indirect production of Lu-177 without the Lu-177m byproduct

– Give precedence to university-based research proposals, including those in partnership with DOE labs

– Work within DOE offices to establish funding for an expanded accelerator research program

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• In 2009, the NSAC Isotope Subcommittee released its Final Report regarding the charges on the Isotope Development and Production for Research and Applications program, which stated:– The current program relies on accelerators and reactors whose primary missions

are not isotope production

• Thus, it is not in a position to provide continuous access to many of the isotopes

– Construct and operate a variable-energy, high-current, multi-article accelerator and supporting facilities that have the primary mission of isotope production

– The most cost-effective option to position the isotope program to ensure the continuous access to many of the radioactive isotopes required is for the program to operate a dedicated accelerator facility

– Given the uncertainties in future demand, this facility should be capable of producing the broadest range of interesting isotopes

• SNMMI supports the Subcommittee’s previous recommendations 18

Isotope Subcommittee’s Previous Recommendations