Development of a high-activity 225Ac/213Bi radionuclide generator for synthesis of clinical doses of 213Bi-labelled biomolecules

The potential of applying 213Bi in targeted alpha therapy (TAT) of cancer and infectious diseases has been demonstrated in a wide body of preclinical studies and in an increasing number of clinical trials. The short-lived alpha emitter (T1/2 = 45.6 min) is conveniently available in clinical settings from 225Ac/213Bi radionuclide generators. Clinical trials on leukemia, neuroendocrine tumors and gliomas have demonstrated the favourable safety profile of TAT with 213Bi as well as the need for preparation of therapeutic doses of up to 6 GBq 213Bi per patient. Consequently 225Ac/213Bi radionuclide generators loaded with several GBq of 225Ac/213Bi are required to minimize the number of radiolabeling procedures and injections per patient. The established 225Ac/213Bi radionuclide generator system is based on the use of the organic cation exchange resin AG MP-50 (Bio-Rad). Standard generators made of 0.3 ml of resin provide constant yield of 213Bi elution and low parent breakthrough when loaded with 225Ac activities up to 1.8 GBq. However, when loaded with higher activities increasing radiolytic degradation of the organic resin leads to deterioration of generator performance. Here we present the development of an optimized generator design that allows the reliable operation at activities of 225Ac/213Bi up to 3 GBq (81 mCi).

BRUCHERTSEIFER Frank;  APOSTOLIDIS Christos;  MIRZADEH Saed;  BOLL Rose;  MURPHY Karen;  MORGENSTERN Alfred; 

2013-06-21

Oak Ridge National Laboratory

JRC82742

https://register.ornl.gov/2013/TATS/index.shtml,    https://publications.jrc.ec.europa.eu/repository/handle/JRC82742,