Abstract 5286: Evaluation of 64Cu-labeled peptide for in vivo imaging of Thomsen-Friedenreich antigen expressing breast carcinomas

Abstract

Abstract Introduction: Thomsen-Friedenreich carbohydrate antigen (TF; Galβ1-3GalNAc) is displayed on cell surface proteins and lipids in ∼90% of adenocarcinomas including those of the breast. We investigated the ability of a peptide, DRD-IVWHRWYAWSPASRI-DRD-NH2 (TF-pep), selected through bacteriophage display to bind breast and prostate carcinoma cells expressing TF. It is hypothesized that TF-pep once radiolabeled with 64Cu, a positron radiation emitter, has the potential to be used as a positron emission tomography (PET) imaging agent for TF expressing breast tumors for diagnostic purposes. Experimental Procedure: A bifunctional-chelator (1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)) was attached to the TF-pep with Gly-Ser-Gly (GSG) spacer. The peptide was radiolabeled with 64Cu in ammonium acetate buffer pH 6.8 at 80oC for 60 minutes. In vitro cell binding studies with both human breast (MDA-MB-435) carcinoma cells, as well as normal breast epithelial (184A1) cells were performed with the radiolabeled peptide. In vivo biodistribution and PET/CT imaging of the tumor with radiolabeled peptide was analyzed in SCID mice bearing MDA-MB-435 tumor xenografts. Results: 64Cu-NOTA-Gly-Ser-Gly-TF-pep peptide bound to human MDA-MB-435 carcinoma cells in a time dependant manner while insignificant binding was observed with normal breast 184A1 cells. In vivo biodistribution studies demonstrated radiolabeled peptide accumulation in MDA-MB-435 tumor-bearing SCID mice (∼1.09 ± 0.34 %, and 0.85 ± 0.06% ID/g in tumor) at 0.5 h and 2 h, respectively. Little accumulation occurred in other organs with the exception of liver (1.12 ± 0.12% ID/g, and kidneys (15.4 ± 1.2% ID/g) at 1 h. Live imaging studies with 64Cu-NOTA-Gly-Ser-Gly-TF-pep (300 μιχρoCi) demonstrated good tumor uptake after 1 h post-injection. Conclusions: The TF-specific peptide once radiolabeled with 64Cu, can function as a non-invasive in vivo tumor imaging agent of human breast and other carcinomas expressing this antigen. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5286. doi:10.1158/1538-7445.AM2011-5286