Targeted alpha therapy with bismuth‐213 and actinium‐225: Meeting future demand

Abstract

Targeted alpha therapy (TAT) is a promising approach for the treatment of cancer. The use of alpha emitters for cancer therapy has two distinct advantages over conventional therapies. The short range of alpha radiation in human tissue (less than 0.1 mm), corresponding to only a few cell diameters, allows selective killing of targeted cancer cells while sparing surrounding healthy tissue. At the same time, the high energy (several MeV) of alpha radiation and its associated high linear energy transfer leads to highly effective cell kill. Consequently, alpha radiation can destroy cells which otherwise exhibit resistance to treatment with beta or gamma irradiation or chemotherapeutic drugs, and can thus offer a therapeutic option for tumors resistant to conventional therapies. Recent results demonstrating the remarkable therapeutic efficacy of alpha emitters to treat various cancers have underlined the clinical potential of TAT. This paper describes the recent clinical experience with 213Bi and 225Ac. In view of the enormous benefit of targeted cancer treatment with alpha emitters, their production will have to be considerably increased beyond current supply capabilities. Alternative production methods based on the irradiation of uranium, thorium, or radium targets at reactors or accelerator facilities have the potential to meet future demand.

Bismuth-213 for Targeted Radionuclide Therapy: From Atom to Bedside

“…Several approaches for 225 Ac and 213 Bi production have been recently reviewed and discussed in detail (Fig. 3) [7,17]. The most utilized strategy is the radiochemical extraction of 225 Ac from 229 Th (T1/2 = 7,317 y) sources originating from the decay of fissile 233 U.…”

“…Most of the 213 Bi and 225 Ac used in clinical tests and research activities worldwide, has so far been produced by this approach [16]. Two examples of 229 Th sources that can produce clinically relevant activities of 225 [24] and cannot meet the growing demand for 225 Ac, but interestingly, it has been reported that stocks will be increased by extraction of additional 229 Th from US legacy wastes [7]. Cyclotron production is an alternative method for 225 Ac production.…”

“…(Fig. 3) [7]. These generators have clinically promising qualities due to the relatively long parent half-life which allows shipment of the generator towards radiopharmacy facilities at long distance.…”

“…1). A fundamental and critical component of a radiometal-based radiopharmaceutical is the chelator, the ligand that binds the radiometal ion in a stable coordination complex so that it can be properly directed to its molecular target in vivo [5][6][7]. The radiopharmaceutical is mostly distributed within the body by the vascular system and allows targeting of a primary tumor and all its metastases.…”

Prostaatspecifiek membraanantigeen radioligandtherapie met alfastralers, een review

“…Daarom wordt er gezocht naar andere methoden om 225 Ac te produceren, bijvoorbeeld in een cyclotron. Naarmate de klinische behoefte aan 225 Ac groeit, wordt de stimulans om alternatieve productiemethoden te ontwikkelen groter [20,21].…”