Production of actinium-225 for alpha particle mediated radioimmunotherapy

Abstract

The initial clinical trials for treatment of acute myeloid leukemia have demonstrated the effectiveness of the alpha emitter 213Bi in killing cancer cells. Bismuth-213 is obtained from a radionuclide generator system from decay of 10-days 225Ac parent. Recent pre-clinical studies have also shown the potential application of both 213Bi, and the 225Ac parent radionuclide in a variety of cancer systems and targeted radiotherapy. This paper describes our five years of experience in production of 225Ac in partial support of the on-going clinical trials. A four-step chemical process, consisting of both anion and cation exchange chromatography, is utilized for routine separation of carrier-free 225Ac from a mixture of 228Th, 229Th and 232Th. The separation of Ra and Ac from Th is achieved using the marcoporous anion exchange resin MP1 in 8 M HNO 3 media. Two sequential MP1/NO 3 columns provide a separation factor of ∼10 6 for Ra and Ac from Th. The separation of Ac from Ra is accomplished on a low cross-linking cation exchange resin AG50-X4 using 1.2 M HNO 3 as eluant. Two sequential AG50/NO 3 columns provide a separation factor of ∼10 2 for Ac from Ra. A 60-day processing schedule has been adopted in order to reduce the processing cost and to provide the highest levels of 225Ac possible. Over an 8-week campaign, a total of ∼100 mCi of 225Ac (∼80% of the theoretical yield) is shipped in 5–6 batches, with the first batch typically consisting of ∼50 mCi. After the initial separation and purification of Ac, the Ra pool is re-processed on a bi-weekly schedule or as needed to provide smaller batches of 225Ac. The averaged radioisotopic purity of the 225Ac was 99.6 ± 0.7% with a 225Ra content of ⩽0.6%, and an average 229Th content of (4 −4 +5)×10 −5%.