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Biodistribution of 212Pb conjugated trastuzumab in mice

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Abstract

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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Acknowledgments

This research was supported in parts by AREVA Med LLC, and the University of Cincinnati. We thank Patrick Maquaire, and Patrick Bourdet for providing assistance with radiolabeling. The authors are grateful for laboratory radiation assistance and safety as kindly provided by Victoria R. Morris, MS, CHP and her professional staff. We wish to thank Dr. Isaiah J. Fidler at the Department of Cancer Biology, University of Texas, M.D. Anderson Cancer Center for providing the PC-3MM2 human prostate cancer cells.

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Authors and Affiliations

  1. College of Engineering and Applied Sciences, University of Cincinnati, 598 Rhodes Hall, Cincinnati, OH, 45221, USA

    N. R. Schneider, M. Lobaugh, P. Sandwall, S. E. Glover, M. Murry & H. B. Spitz

  2. Division of Hematology-Oncology, University of Cincinnati Cancer Institute, Cincinnati, OH, 45267, USA

    Z. Tan, P. Chen, L. Cui & Z. Dong

  3. AREVA Med LLC, Bethesda, MD, 20816, USA

    J. Torgue

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  1. N. R. Schneider
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  2. M. Lobaugh
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  3. Z. Tan
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  4. P. Sandwall
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  5. P. Chen
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  6. S. E. Glover
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  7. L. Cui
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  8. M. Murry
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  9. Z. Dong
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  10. J. Torgue
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  11. H. B. Spitz
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Correspondence to N. R. Schneider.

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Schneider, N.R., Lobaugh, M., Tan, Z. et al. Biodistribution of 212Pb conjugated trastuzumab in mice. J Radioanal Nucl Chem 296, 75–81 (2013). https://doi.org/10.1007/s10967-012-2243-7

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  • DOI: https://doi.org/10.1007/s10967-012-2243-7

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