REDC Product Development and Cf Program

Nuclear Medicine Program

Alpha Emitting Radioisotopes for Tumor Therapy

Alpha particles are of considerable interest for radioimmunotherapy applications since their short range in soft tissue is limited to only a few cell diameters. The delivery of such high energy in such a small volume, or high-linear-energy-transfer (LET), makes alpha particles especially well suited for targeting micrometastatic disease and single tumor cells such as leukemia and other blood-borne disease. The bismuth-213 radioisotope is of special interest because of its unique nuclear properties, which include a short 45 minute half-life and high energy (8.4 MeV) alpha-particle emission.  Its unique availability from the actinium-225/bismuth-213 generator system makes this radioisotope particularly well suited for medical use.  The actinium-225 is formed from radioactive decay of radium-225, the decay product of thorium-229, which is obtained from decay of uranium-233. The National depository of uranium-233 is at ORNL, and we have developed effective methods for obtaining thorium-229 (half-life 7340 years) as our feed material to routinely obtain actinium-225.

The very short 45 minute half-life of bismuth limits its use, however, only when attachment to a carrier molecule can be conducted very quickly and the targeting is rapid following intravenous administration, such as the clinical treatment of acute myeloid leukemia, as described later, where trials are being conducted at the Memorial Sloan Kettering Cancer Center in New York.  The actinium-225 used for the generators which provide the bismuth-213 for these studies is provided from ORNL.  We are also conducting research with alpha emitting radioisotopes such as bismuth-213.  Radioimmunotherapy  with alpha particles has the advantages of high energy deposition (~ 100 KeV/mm) in a short path length (< 100 m), which produces significant cellular damage  close to the site of radioisotope deposition.  Several alpha-particle emitting radioisotopes have been studied for therapy and the antibody-targeted bismuth-213 for treatment of leukemia and intracranial placement of astatine-211 for adjuvant therapy after surgery for brain tumors. 

Research at ORNL has shown that monoclonal antibodies  targeting bismuth-213 to lung vasculature is also successful for the therapy of lung tumors in mice. Bismuth-213 decays with a half-life of 46 minutes and emits very energetic alpha particles.  (~ 8 MeV).  Carrier-free bimuth-213 is obtained from the actinium-225/bismuth-213 generator system.  The actinium-225 parent (half-life = 10 days) is obtained from decay of thorium-229 (half-life 7,340 years). The majority of the available thorium-229 stock has been recovered from the nuclear waste material which has been stored at ORNL for about 30 years.  Actinium-225 batches of up to 40 mCi are available for sale through the ORNL Isotope Business Office on a bi-monthly schedule and smaller quantities are available on a weekly  schedule. 

Return to Program page

This site was updated 03/15/2005