American Chemical Society MeetingBoston, August 22-26, 2010

Current and Future Needs for Isotopes Critical to Research and Industry

Wolfgang Runde, Ph.D.National Isotope Development Center,

Associate Directorrunde@lanl.gov

Robert W. Atcher, Ph.D., MBANIDC, Director

U.S. DOE Isotope ProgramOffice of Nuclear Physics

LA-UR 10-06310

Needs for Isotope Products

• NAS Panel report on training and needs in nuclear and radiochemistry (1983)

• NAS Panel report on Isotope Production needs (1986)• Workhop on dedicated accelerator (Los Alamos National

Laboratory, 1988)• SNM White paper on need for dedicated accelerator (1990).• Input from research community, scientific organizations, private

sector (IsoSolutions’ Market Study , 2002)• Isotope inquiries submitted to Isotope Appplications Program's

Sales Office• Radionuclide Availability: Research and Beyond (SNM, Jan

2004)• Numerous workshops on the topic in the last few years

Needs for isotope products

• Advancing Nuclear Medicine Through Innovation (NAS, September 2007):– Improve domestic medical radionuclide

production– Research isotope production– Train next generation of radiochemists and

nuclear medicine scientists– Renew funding for nuclear medicine research

within the DOE portfolio• OBER funding restored• FY2011 – move to Office of Nuclear Physics

Need for Isotope Products

Workshop on The Nation’s Need for Isotopes: Present and Future (ONP, 2008)

• NSACI Report, 2009• Volume 1, Immediate needs for production• Volume 2, Strategic needs

• Dedicated accelerator• Re-establish enrichment capability

Isotope Supply IssuesDomestic Supply

Arsenic-73Californium-252Cobalt-60 (NRU, Canada)Fluorine-18Germanium-68/Gallium-68Holmium-166Indium-111Lutetium-177 Palladium-103Phosphorus-32, phosphorus-33Radium-224/Bismuth-212Radium-223 & daughtersSamarium-153Strontium-82/Rubidium-82Thallium-201Tin-117mTungsten-188/Rhenium-188Yttrium-90 (NRU, Canada)

Foreign SupplyCesium-131Cobalt-57Gadolinium-153Iodine-125, iodine-131 (NRU)Molybdenum-99/Technetium-99m

We’ll save this for another symposium

Strontium-89Xenon-133 (NRU)

Little or No SupplyActinium-225Astatine-211Bromine-77Copper-64 (?),67Gold-198Iodine-124Platinum-195mYttrium-86Zirconium-89

Isotopes Supplied by DOE Isotope ProgramDomestic Supply

Arsenic-73Californium-252Cobalt-60 (NRU, Canada)Fluorine-18Germanium-68/Gallium-68Holmium-166Indium-111Iodine-123Lutetium-177 Palladium-103Phosphorus-32, phosphorus-33Radium-224/Bismuth-212Radium-223/daughtersSamarium-153Strontium-82/Rubidium-82Thallium-201Tin-117mTungsten-188/Rhenium-188Yttrium-90 (NRU, Canada)

Foreign SupplyCesium-131Cobalt-57Gadolinium-153*Iodine-125, iodine-131 (NRU)Molybdenum-99/Technetium-99mStrontium-89Xenon-133 (NRU)

Little or No SupplyActinium-225Astatine-211Bromine-77Copper-64**,67*Gold-198Iodine-124Platinum-195mYttrium-86Zirconium-89

Origin and Mission of the Isotope Program

Congress entrusted the U.S. Department of Energy with the authority and responsibility to produce stable and radioactive isotopes for medicine, science, and industrial applications (Atomic Energy Act, 1954).

MISSION:

Produce and distribute radioactive and stable isotopes, associated byproducts, surplus materials, and related isotope services.

Maintain the infrastructure required to supply isotope products and related services.

Essential Facilities for Isotope Production

Essential facilities and equipment were defined as those located at the sites where domestic isotope production and processing currently take place for the Isotope Production and Applications Program

Originally DOE considered five production facilities essential to the program: Tritium Facility – SRS LANSCE/100 MeV Isotope Production Facility (IPF) – LANL 200 MeV linac/Brookhaven Linac Isotope Producer (BLIP) –

BNL High Flux Isotope Reactor (HFIR) – ORNL Advanced Test Reactor (ATR) – INL

Network of Domestic Production Sites

Idaho – ATR:Ir-192 – Industrial non-destructive

analysisCo-60 – Sterilization of surgical

equipment and blood

UC Davis – CrockerMcClellan: I-125

Richland:Sr-90 – Y-90 gen for

cancer therapy

Brookhaven – BLIP:Ge-68 – Calibration sources for PET

equipment; Antibody labelingSr-82 – Rb-82 gen used in cardiac

imaging

Los Alamos – LANSCE/IPF:Ge-68 – Calibration sources for PET

equipment; Antibody labelingSr-82 – Rb-82 gen used in cardiac imagingAm-241 – Oil well logging

Columbia – MURR:Lu-177 – Treatment of ovarian and colon cancerHo-166 – Treatment of multiple myeloma

and rheumatoid arthritisP-32 – SPECT imaging Savannah River:

He-3 – He-Li and He-Ne lasers– Fuel source for fusion reactors– Research: Property studies of

super fluids

Denton:Cu-67 – Cancer therapy

Oak Ridge – HFIR:Se-75 - Industrial NDA; Protein

studiesCf-252 - Industrial source W-188 - Cancer therapyStable Isotopes Inventory:Top 10 stable isotopes sold over the last 5 years:Ca-48, Ga-69, Rb-87, Cl-37, Pt-195, Nd-146, Sm-149, Ru-99, Zr-96Inventory:Ac-225 - Cancer therapyNi-63 - Explosives detection

Reactor Sites: ORNL and ATR

Advanced Test Reactor (ATR) at INL:

– Moderately high neutron flux (≤8x1014 n/cm2 s)

– Hydraulic tube to be installed for short term irradiations

– Hot cell facilities– Key Isotope: Co-60

High Flux Isotope Reactor (HFIR) at ORNL:

– High neutron flux (≤3x1015

n/cm2 s)– Multiple hydraulic tubes– Several hot cell facilities– Key Isotopes: Cf-252, Ni-

63, Se-75, W-188

University of Missouri Research Reactor Center (MURR)

10 MW, largest university research reactorMini-HFIR designBeryllium reflector, light water moderated and cooled pool-typeProduces more than 40 different isotopes, including 177Lu, 186Re, 153Sm, 90Y, 32P, 33P, 192Ir, 166HoCore: 28 cm-dia.X 61 cm tall Flux trap with peak flux of6x1014 n/cm2sec

6.2 kg loading of 235U (HEU)Operates year-round; supports many faculty and students

Commercial CyclotronsAccelerates charged hydrogen atoms (protons, deuterons, alphas)Energies 13-40 MeV and up to 70 MeV, current to 2 mAEfficient, reliable, operational expenses knownOperational aspects well know after decades of use in commercial production

Compact French 65 MeV cyclotron for proton and neutron therapy.

For production of proton-rich isotopes, including: 18F, 82Sr, 64Cu, 67Cu, 15O, 11C, 76Br, 77Br, 124I, 86Y, 66Ga, 60Cu, 61Cu, 68Ge, 82Sr, 89Zr, 203Pb, 211At

Commercial cycltrons

Several commercial manufacturers:– Ion Beam Applications (IBA, Belgium)– Ebco Technologies (now ACS, Canada)– Best Technologies– Sumitomo Heavy Industries, Ltd. (Japan)– General Electric - PET (United States)– Siemens - PET (Germany)

High-Energy Accelerators: BLIP and IPF

Isotope Production Facility (IPF) at LANL:

– 100 MeV proton beam– Well-equipped hot cell facility– Available 30-40 weeks per year– Main isotopes: Ge-68, Sr-82– R&D: As-73/74, Ac-225, Se-72

Brookhaven Linac Isotope Producer (BLIP) at BNL:

– 200 MeV proton beam– Hot cell facility– Target insertion and retrieval– Main isotopes: Ge-68, Sr-82– R&D: Cu-67, Y-88– Availability an issue

International Partnerships

Institute for Nuclear Research (INR), Russia: – 160 MeV beam energy, 100 µA beam current

iThemba Labs, South Africa: – 66 MeV beam energy, 120 µA beam current

Key Isotopes Produced and Distributed

Maximum QuantityIsotope Half Life Shipped in Type A Produced Application

Cf-252 2.6 y, α .02 Ci Reactor Neutron sourcescancer therapy

Cd-109 32.2 y , γ 27 Ci Both reactor X-ray instrumentaccelerator calibration

Co-60 5.27 y , γ 10.8 Ci Reactor Sterilization

Sr-82 25-d, positron 5.41 Ci Accelerator Cardiac imaging

W-188 69-d , β/γ 5.41 Ci Reactor Cancer Treatment

Ge-68 Calibration sources forPET equipment, antibody labeling

Na-22 A positron-emitter used in various applications

Sr-82 Rb-82 for Cardiac imaging

Accelerator IsotopesCf-252 Cancer therapyNi-63 Gas sensing devicesW-188 Re-188 for prevention of

arterial restenosis, Bone pain from cancer

Se-75 GAMMA Radiography sources

Reactor Isotopes

Isotopes That Save Lives

Positron Emission Tomography (PET)

• 82Sr/82Rb – myocardial imaging. 82Rb used in cardiac perfusion studies with PET. Approximately 10000 patients per month benefit from imaging studies. LANL is meeting about 75% of the US demand.

• 68Ge – attenuation correction and radiopharmaceutical research. Positron emitter used in calibration sources for PET scanners. There are more than 800 PET centers in the United States, and over 1200 globally.

Ge-68 used as PETcalibration source

Rb-82 used for PET imaging

Medical Radioisotope Research

• Isotope Production R&D– Rediscovery of “old” isotopes– New production methods

• Isotope Delivery Systems– Biomedical generators (Ge/Ga-68; Se/As-

72)– Radiopharmaceutical synthesis– Collaborative radiopharmaceutical clinical

studies (UNM, IAS, UC Davis Med Inst.)

• Labeled Molecule Behavior in Biological Systems– Leverages molecular biology capability– Leverages cell biology capability– Handoff to NIH funded investigations

Isotope Developments: Ga-68

• Ga-68 generator technology being improved to provide superior product

• Animal imaging

• Studies using DOTA-peptide bound to Ga-68 (t1/2 = 68.3 min)

• Suited to short biologic half life targeting molecules

• An option to F-18

MRI/PET using 68Ga-DOTA-TOCJ. Fitzsimmons et al.

Isotope Developments: Ac-225

N N

NNN

HO

O

HO O

OH

O

OHO

S

HNPEI

N N

NN N

HO

O

HO O

OH

O

OHO

S

HNPEI

225Ac225Ac

225Ac-DOTA-PEIDOTA-PEI

Reaction Conditions0.2 M buffer, pH=6.0, 77º C 2-4

hours

PurificationBio Rad size exclusion column (10DG)

Incorporation yields of 225Ac:Sodium bicarbonate 42-53%Phosphate buffered saline 67%Ammonium acetate 79%

Fitzsimmons, Atcher et al.

Chemical and Materials Laboratory at ORNL

Laboratories at ORNL provide unique services and dispense over 200 different stable enriched and long-

lived isotopes in various of chemical and physical forms:

See Isotope Newsletter Fall/Winter 2007

– Metallurgical, ceramic, and high vacuum processing methods– Pyrochemical Conversion: oxide to high-purity metal– Arcmelting and alloying Hot and cold rolling– Preparation of cold-rolled foils from air-reactive metals– Drop casting– Wire rolling/swaging (hot or cold)– Target fabrication

Concluding Remarks

Isotope production capability in the U.S. is improving But we are dependent on foreign supplies and still lack ability to

produce the major medical isotopes: 99Mo/99mTc, 131I, 125I (a world crisis)

The Isotope Program has unique resources needed to produce and distribute isotopes other than Pu-238 (NASA) and Mo-99

We still lack substantial production capability and capacity for important medical and industrial radioisotopes (67Cu, 211At, 225Ac/213Bi, and 241Am) and isotopes for miniature power sources (148Gd, high s.a. Sr-90, Pm-147)

Portfolio needs to become more diverse to engage fields besides nuclear medicine

Transfer of the Isotope Program to Office of Science offers new opportunities for isotope R&D, SBIR/STTR and training