Production of actinium-225 for alpha particle mediated radioimmunotherapy

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 HNO3 media. Two sequential MP1/NO3 columns provide a separation factor of ∼106 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 HNO3 as eluant. Two sequential AG50/NO3 columns provide a separation factor of ∼102 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%.