Application of <sup>212</sup>Pb for Targeted α-particle Therapy (TAT): Pre-clinical and Mechanistic Understanding through to Clinical Translation

Kwon Yong; Martin Brechbiel; Kwon Yong; Martin Brechbiel

doi:10.3934/medsci.2015.3.228

AIMS Medical Science

2015, Volume 2, Issue 3: 228-245. doi: 10.3934/medsci.2015.3.228

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Review

Application of ²¹²Pb for Targeted α-particle Therapy (TAT): Pre-clinical and Mechanistic Understanding through to Clinical Translation

Kwon Yong ,
Martin Brechbiel ^,

Radioimmune & Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda MD, USA

Received: 20 April 2015 Accepted: 12 August 2015 Published: 18 August 2015

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 of ²¹²Bi and serves as an in vivo generator of ²¹²Bi. ²¹²Pb has demonstrated significant utility in both in vitro and in vivo models. Recent evaluation of ²¹²Pb-TCMC-trastuzumab in a Phase I clinical trial has demonstrated the feasibility of ²¹²Pb in TAT for the treatment of ovarian cancer patients. This review highlights progress in radionuclide production, radiolabeling chemistry, molecular mechanisms, and application of ²¹²Pb to targeted pre-clinical and clinical radiation therapy for the management and treatment of cancer.
- targeted α-therapy (TAT),
- ²¹²Pb-Radioimmunotherapy (RIT),
- bio-vector,
- trastuzumab,
- cancer
Citation: Kwon Yong, Martin Brechbiel. Application of 212Pb for Targeted α-particle Therapy (TAT): Pre-clinical and Mechanistic Understanding through to Clinical Translation[J]. AIMS Medical Science, 2015, 2(3): 228-245. doi: 10.3934/medsci.2015.3.228

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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 of ²¹²Bi and serves as an in vivo generator of ²¹²Bi. ²¹²Pb has demonstrated significant utility in both in vitro and in vivo models. Recent evaluation of ²¹²Pb-TCMC-trastuzumab in a Phase I clinical trial has demonstrated the feasibility of ²¹²Pb in TAT for the treatment of ovarian cancer patients. This review highlights progress in radionuclide production, radiolabeling chemistry, molecular mechanisms, and application of ²¹²Pb to targeted pre-clinical and clinical radiation therapy for the management and treatment of cancer.

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