Preclinical evaluation of the breast cancer cell-binding peptide, p160

Purpose: Selective delivery of drugs into the target tissue is expected to result in high drug concentrations in the tissue of interest and therefore enhanced drug efficacy. To develop a peptidebased radiopharmaceutical, we investigated the properties of a peptide with affinity for human breast cancer, which has been selected through phage display. Experimental Design: The bioactivity of the p160 peptide (VPWMEPAYQRFL) was evaluated in vitro and in vivo. The specific binding to human breast cancer MDA-MB-435 cells was confirmed in competition experiments. Internalization of the peptide was investigated with confocal microscopy. Furthermore, the biodistribution of I-131-labeled p160 was studied in tumor-bearing mice. In vivo stability was evaluated at different periods after tracer administration using high-performance liquid chromatography analysis. Results: The binding of I-125-labeled p160 was inhibited up to 95% by the unlabeled pepticle with an IC50 value of 0.6 mu mol/L. In addition, 40% of the total bound activity was found to be internalized into the human breast cancer cells. Although a rapid degradation was seen, biodistribution studies in nude mice showed a higher uptake in tumor than in most of the organs. Perfusion of the animals caused a reduction of the radioligand accumulation in the healthy tissues, whereas the tumor uptake remained constant. A comparison of [I-131]p160 with a I-131-labeled Arg-Gly-Asp pepticle revealed a higher tumor-to-organ ratio for [I-131] p160. Conclusions: p160 has properties that make it an attractive carrier for tumor imaging and the intracellular delivery of isotopes or chemotherapeutic drugs.