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

In contrast to external high energy photon or proton therapy, targeted radionuclide therapy (TRNT) is a systemic cancer treatment allowing targeted irradiation of a primary tumor and all its metastases, resulting in less collateral damage to normal tissues. The α-emitting radionuclide bismuth-213 ((213)Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with (213)Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of (225)Ac and its daughter (213)Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth and general considerations for designing a (213)Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving (213)Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.