Alternative Methods for Production of Ac225 James Harvey 1, Jerry A. Nolen 3, Thomas Kroc 4, Itacil Gomes 5, E. Philip. Horwitz 2, Daniel R. McAlister 2 Workshop on Applications of High Intensity Proton Accelerators October 19-21, 2009 Fermi National Accelerator Laboratory, Batavia, IL, USA 1 NorthStar Medical Radioisotopes, LLC, Madison, WI 2 PG Research Foundation, Lisle, IL 3 Argonne National Laboratory, Argonne, IL 4 Fermi National Accelerator Laboratory, Batavia, IL 5 I.C. Gomes Consulting, Naperville, IL “Enabling the future of nuclear medicine”

Ac225 Research - Ac225/Bi213 is a promising Alpha Immunotherapy (AIT) radioisotope - Current clinical work are underway in (among others): - AML - Metastatic melanona - Gastric cancer - HIV - World supply limited today to about 1,000mCi per year - ~650mCi from ORNL - ~350mCi from ITU (not for sale)

“Enabling the future of nuclear medicine” Ac225 Research

“Enabling the future of nuclear medicine” Ac225 Research Above clinical research performed under an approved institutional IRB at a licensed animal vivarium; work described herein does not include animal testing

“Enabling the future of nuclear medicine” Ac225 Needs YearAmount (mCi) , , , , ? 2014? Note: Chart does not include new R&D that could be started as result of supply expansion, only known needs. Estimates in out years vary by ±50% depending on whether the approved treatment is with Ac225 or with Bi213.

“Enabling the future of nuclear medicine” Ac225 Needs USES FOR 233U, Forsberg, C.W., Chemical Technology Division, Oak Ridge National Laboratory, Briefing for U.S. Department of Energy, Oak Ridge, Tennessee, March 22, 2000

“Enabling the future of nuclear medicine” Ac225 Sources Extracted from existing Th229 stock ORNL – 150mCi Th229 (on-going; ~600mCi Ac225 annually) INL – 27MT LWBR fuel – ~14MT unirradiated + ~13MT “lightly” irradiated (~5,000mCi/month Ac225 ) Chemical separation of Th229 from existing U233 stock (~45g Th229 yielding ~6,000mCi/month Ac225) Cyclotron production via Ra226(p,2n)Ac225 (~200mCi/month/cyclotron) Photonuclear transmutation of Ra226 via Ra226(γ,n)Ra225→Ac225 (~400mCi/month/LINAC) Reactor production of Th229 (Ra226→Th229 or Th228(n, γ)Th229 High Energy Proton Spallation of Th232 (~10,000+mCi/month potential)

“Enabling the future of nuclear medicine” CRADA at INL

“Enabling the future of nuclear medicine” CRADA at INL Status Phase 1 successfully completed in 2008 with successful bench scale production Ac225 Pilot plant preliminary design established ~13MT of unirradiated LWBR fuel transferred to NTS for disposal in 2008 – 1MT remains with half that also dispositioned for NTS disposal; irradiated material still at INL Potential route using LWBR fuel to Ac225 questionable

“Enabling the future of nuclear medicine” U233 Initiative Requested small portion (15Kg) of U233 stored in Bldg 3019 to demonstrate process for extraction of Th229 capable of production of 300mCi/month Ac225 within 1 year

“Enabling the future of nuclear medicine” U233 Initiative Bldg 3019 U233 stocks under contract for down blending beginning in 2012 IG Report: “…..the inventory of uranium-233 is being disposed of because there is a lack of programmatic authority to maintain the material and the infrastructure necessary to continue extracting the actinium and bismuth.” Likely will require Congressional intervention to save this source of Th229(Ac225)

“Enabling the future of nuclear medicine” Alternative Production Routes Cyclotron production via Ra226(p,2n)Ac225 - Demonstrated on a modest scale but not proven commercially viable yet (~200mCi/month/cyclotron) Photonuclear transmutation via Ra226(γ,n)Ra225→Ac225 - Demonstrated on a very small scale but not proven commercially viable yet (~400mCi/month/LINAC) Reactor production of Th229 (Ra226→Th229) or (Th228→Th229) - Demonstrated on a very small scale but not proven commercially viable yet (?mCi/month) High Energy Proton Spallation of Th232 - Proposal to DOE to pursue submitted May Selected for funding; start in November 2009

“Enabling the future of nuclear medicine” High Energy Proton Spallation of Th232 -Effort will utilize FNAL to study production at 2 available energies - 400Mev - 8Gev - Irradiations at FNAL with target (Th232) transfer to ANL for processing - Decay to allow short lived radioisotopes to decay - Ac226 is 1.2 days t ½ - Quality comparison to currently available Ac225 (ORNL) - mAb labeling to prove equivalency of Bi213 from either source - Potential with dedicated irradiations to produce up to 1,000mCi/day - a small fraction of the beam with energy >200MeV could be a prolific source of Ac225

“Enabling the future of nuclear medicine” Summary DOE sources for Ac225: - LWBR processing – now questionable - Bldg 3019 U233 – questionable viability Alternative sources: - Cyclotron and Photonuclear need Ra226 (mg to gram amounts) - Th229 production needs Ra226 (gram) and high flux reactor (DOE) - Th232 spallation could resolve supply challenges - demonstration underway beginning in Nov beam with energy >200MeV could be a prolific source of Ac225

“Enabling the future of nuclear medicine” Discussion Acknowledgements: ANL work is supported by the U.S. Department of Energy, Office of Nuclear Physics, under Contract No. DE-AC02-06CH Fermi National Accelerator Laboratory is operated by Fermi Research Alliance, LLC under Contract No. DE-AC02-07CH11359 with the United States Department of Energy. New work to be funded by DOE Office of Science