Abstract
Targeted α-particle therapy (TAT), in which an α-particle emitting radionuclide is specifically directed to a biological target, is gaining more attention to treat cancers as new targets are validated. Bio-vectors such as monoclonal antibodies are able to selectively transport α-particles to destroy targeted cancer cells. TAT has the potential for an improved therapeutic ratio over β-particle targeted conjugate therapy. The short path length and the intense ionization path generated render α-emitters suitable for treatment and management of minimal disease such as micrometastases or residual tumor after surgical debulking. (212)Pb is the longer-lived parent radionuclide of (212)Bi and serves as an in vivo generator of (212)Bi. (212)Pb has demonstrated significant utility in both in vitro and in vivo models. Recent evaluation of (212)Pb-TCMC-trastuzumab in a Phase I clinical trial has demonstrated the feasibility of (212)Pb in TAT for the treatment of ovarian cancer patients. This review highlights progress in radionuclide production, radiolabeling chemistry, molecular mechanisms, and application of (212)Pb to targeted pre-clinical and clinical radiation therapy for the management and treatment of cancer.