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 (²¹³Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with²¹³Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of²²⁵Ac and its daughter²¹³Bi 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 a²¹³Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving²¹³Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.