(177)Lu/ (90)Y intermediate-affinity monoclonal antibodies targeting EGFR and HER2/c-neu: preparation and preclinical evaluation.

摘要: The epidermal growth factor receptor (EGFR) is a rational target of anticancer therapies due to its overexpression in variety malignant epithelial tumors. Nevertheless, this antigen also present normal tissues. Consequently, monoclonal antibodies which selectively bind EGFR-overexpressing tumors will be choice drug candidates for development radioimmunoconjugates (RIC). Nimotuzumab (h-R3) and trastuzumab are (mAbs) would preferentially tissues with EGFR HER2 overexpression, respectively. In chapter, we describe preparation evaluation the targeting properties RIC formed by 177Lu/90Y EGFR- HER2/c-neu-overexpressing mAbs were labeled n.c.a. using bifunctional chelating agents. binding toxicity evaluated vitro cell lines varying expression. vivo tumor mice bearing colorectal (SNU-C2B) A431 xenografts. RICs prepared specific activities up 2 GBq/mg without significant loss biological activity. 90Y-h-R3/trastuzumab increased inhibition compared unmodified or 90YCl3 alone antigen. 177Lu-h-R3 showed significantly higher uptake (22.8 ± 3.1% ID/g) than SNU-C2B (8.8 4.1% xenografts at 72 h post injection, indicating strong association between expression levels.