title: Application of212Pb for Targeted α-particle Therapy (TAT): Pre-clinical and Mechanistic Understanding through to Clinical Translation.
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.212Pb is the longer-lived parent radionuclide of212Bi and serves as an in vivo generator of212Bi.212Pb has demonstrated significant utility in both in vitro and in vivo models. Recent evaluation of212Pb-TCMC-trastuzumab in a Phase I clinical trial has demonstrated the feasibility of212Pb in TAT for the treatment of ovarian cancer patients. This review highlights progress in radionuclide production, radiolabeling chemistry, molecular mechanisms, and application of212Pb to targeted pre-clinical and clinical radiation therapy for the management and treatment of cancer.
authors: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
authors: Kwon
authors: K
authors: Yong
authors: Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda MD, USA.
authors: Martin
authors: M
authors: Brechbiel
keywords: 212Pb-Radioimmunotherapy (RIT); bio-vector; cancer; targeted α-therapy (TAT); trastuzumab