Theranostics, Gallium-68, and Other Radionuclides

Abstract

The epidermal growth factor receptor (EGFR) is a rational target of anticancer therapies due to its overexpression in a variety of malignant epithelial tumors. Nevertheless, this antigen is also present in normal tissues. Consequently, monoclonal antibodies which selectively bind to EGFR-overexpressing tumors will be choice drug candidates for development of radioimmunoconjugates (RIC). Nimotuzumab (h-R3) and trastuzumab are monoclonal antibodies (mAbs) which would preferentially target tissues with EGFR and HER2 overexpression, respectively. In this chapter, we describe preparation and evaluation of the targeting properties of RIC formed by 177Lu/90Y and monoclonal antibodies which selectively target EGFR- and HER2/c-neu-overexpressing tissues. mAbs were labeled with n.c.a. 177Lu/90Y using bifunctional chelating agents. RIC binding properties and toxicity were evaluated in vitro using cell lines with varying antigen expression. In vivo tumor targeting properties of RIC were evaluated in mice bearing colorectal (SNU-C2B) and A431 tumor xenografts. RICs were prepared with specific activities up to 2 GBq/mg without significant loss in biological activity. 90Y-h-R3/trastuzumab increased cell growth inhibition compared with unmodified mAbs or 90YCl3 alone in cell lines with overexpres- sion of the target antigen. 177Lu-h-R3 showed significantly higher uptake in A431 D. R. Beckford Vera (&)  S. Eigner  K. E. Henke  F. Melichar  M. Beran Department of Radiopharmaceuticals, Nuclear Physics Institute, Academy of Sciences of the Czech Republic, 250 68 Rez, Prague, Czech Republic e-mail: denis.beckford@gmail.com R. L. Montaña Department of Radiopharmacy, Center of Isotopes, Guanabacoa, Ciudad de La Habana, Cuba R. P. Baum and F. Rösch (eds.), Theranostics, Gallium-68, and Other Radionuclides, Recent Results in Cancer Research 194, DOI: 10.1007/978-3-642-27994-2_16,  Springer-Verlag Berlin Heidelberg 2013 301