Radioimmunotherapy (RIT), using an alpha-emitter provides an efficient tool for cancer therapy, far better suited than �--emitters for treating small tumor burden and micrometastases. Pb-212 RIT pre-clinical trials have been performed in animal models ultimately directed towards translation to an appropriate clinical trial. Along this road, assumptions and standards regarding mechanisms of action were made, yet a dearth of in vivo data exists for their basis.  In addition to providing an overview of Pb-212 RIT past, present, and future, results from studies elucidating mechanisms by alpha-particle RIT, specifically effects from Pb-212-TCMC-trastuzumab, e.g., induction of DNA double strand breaks, blockage of DNA damage repair by interference with RAD51, and induction of cell death, but not via caspase-3 apoptosis, will be presented to define a better understanding of the in vivo mechanism of alpha-particle RIT to generate information to optimize usage of chemotherapeutics in combination with alpha-particle RIT.

Pb-212 radioimmunotherapy – observations along a lengthy long road forward

243rd National Meeting (2012)

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