Biodistribution of [sup.212]Pb conjugated trastuzumab in mice

The biodistribution in mice of [sup.212]Pb-trastuzumab, a HER2 targeting immunoglobulin (monoclonal antibody), was investigated for its potential as a therapeutic agent with immunocytotoxic applications. [sup.212]Pb-trastuzumab is an alpha-emitting radioimmunoconjugate that can deliver a shortrange, high linear energy transfer (LET) radiation dose to targeted tissue. [sup.212]Pb is an attractive isotope for medical applications because it is has a short half-life (10.64 h), and one of its decay products ([sup.212]Po) emits a very high LET alpha-particle (E = 8.78 MeV). Radiolabeled trastuzumab was found to be pure, functional, and intact by both ELISA and SDS-PAGE evaluation. The uptake and biodistribution of [sup.212]Pb-trastuzumab was determined as a percentage of the injected dose by analysis of nine different organs obtained from serially sacrificed male nude mice bearing orthotopic tumors of PC-3MM human prostate carcinoma. High-resolution gamma spectrometry was used to determine the content of [sup.212]Pb in each organ at several fixed times post intravenous injection. Although the PC-3MM2 cells express limited HER2 receptors, approximately 8% of injected dose was observed in the tumor at 12 h post IV injection. Results of this biodistribution study support further investigation of radiolabeled [sup.212]Pb-trastuzumab, radiobiological organ microdosimetry, and optimal dosing regimens for trastuzumab as a therapeutic agent. Keywords Biodistribution * [sup.212]Pb-trastuzumab * Monoclonal antibody * Dosimetry * Radioimmunoconjugate