Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Pharmacology & Pharmacy, bismuth-213, targeted radionuclide therapy, targeted alpha therapy, radiopharmaceutical, bifunctional chelator, vector molecule, EXPRESSING NEUROENDOCRINE TUMORS, PHASE-I TRIAL, ALPHA-THERAPY, MOUSE MODEL, ACTINIUM-225 (AC-225)-LINTUZUMAB, AC-225/BI-213 GENERATOR, PARTICLE IMMUNOTHERAPY, BIOLOGICAL EVALUATION, DOSIMETRY ESTIMATE, PROSTATE-CANCER, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences

Abstract:

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 with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi 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 213Bi-radiopharmaceutical are provided. Finally, we provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.