Biodistribution of 212Pb conjugated trastuzumab in mice

October 18, 2012

Biodistribution of 212Pb conjugated trastuzumab in mice

Journal of Radioanalytical and Nuclear Chemistry

October 2012

N. R. Schneider, M. Lobaugh, Z. Tan, P. Sandwall, P. Chen, S. E. Glover, L. Cui, M. Murry, Z. Dong, J. Torgue, H. B. Spitz …


The biodistribution in mice of 212Pb-trastuzumab, a HER2 targeting immunoglobulin (monoclonal antibody), was investigated for its potential as a therapeutic agent with immunocytotoxic applications. 212Pb-trastuzumab is an alpha-emitting radioimmunoconjugate that can deliver a short-range, high linear energy transfer (LET) radiation dose to targeted tissue. 212Pb is an attractive isotope for medical applications because it is has a short half-life (10.64 h), and one of its decay products (212Po) 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 212Pb-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-3MM2 human prostate carcinoma. High-resolution gamma spectrometry was used to determine the content of 212Pb 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 212Pb-trastuzumab, radiobiological organ microdosimetry, and optimal dosing regimens for trastuzumab as a therapeutic agent.

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