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Preclinical Evaluation of the Breast Cancer Cell-Binding Peptide, p160

Authors' Affiliations: ¹ Clinical Cooperation Unit Nuclear Medicine and Departments of ² Cytogenetics and ³ Radiopharmaceutical Chemistry, German Cancer Research Center; ⁴ Department of Nuclear Medicine and ⁵ Medical Biophysics, Institute for Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany

Requests for reprints: Uwe Haberkorn, Department of Nuclear Medicine, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. Phone: 49-6221-567732; Fax: 49-6221-565463; E-mail: uwe_haberkorn{at}med.uni-heidelberg.de.

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 peptide-based 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 ¹³¹I-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 ¹²⁵I-labeled p160 was inhibited up to 95% by the unlabeled peptide with an IC₅₀ value of 0.6 µmol/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 [¹³¹I]p160 with a ¹³¹I-labeled Arg-Gly-Asp peptide revealed a higher tumor-to-organ ratio for [¹³¹I]p160.

Conclusions: p160 has properties that make it an attractive carrier for tumor imaging and the intracellular delivery of isotopes or chemotherapeutic drugs.

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