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Radiolabelled peptide heterodimer to improve breast and prostate cancer diagnosis by positron emission tomography

¹ Département de Médecine Nucléaire et Radiobiologie, Université de Sherbrooke, Sherbrooke, Quebec, Canada

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Objectives: In recent years, a variety of receptors such as gastrin releasing peptide receptors (GRPR) and neuropeptide Y1 receptors (NPY1R) have been shown to be highly overexpressed in a large proportion of breast and prostate cancers making these receptors prime candidates for diagnostic applications. The purpose of this study was to develop dual action Cu-64 radiolabelled peptides for PET imaging.

Methods: [D-Tyr6,β-Ala11,Thi13,Nle14]BBN(6-14) (Mantey et al. J Biol Chem 1997;272:26062–71) and a truncated NPY analog, also called BVD-15(Balasubramaniam et al. J Med Chem 2001;44:1479), were selected as peptide segments for establishing the optimal heterodimers arrangement for GRPR/NPY1R targeting. DOTA chelator was selected for Cu-64 peptide labelling. We prepared head-to-tail peptide heterodimers and measured their binding affinities to both receptors. Competitive binding assays were performed on human breast cancer cell lines (MCF-7 and T47D) with peptide monomers and heterodimers to investigate these new radiopharmaceuticals.

Results: We achieved excellent GRPR affinities (Ki=1-4 nM) with the heterodimers having the C-terminal group of BVD-15 and the N-terminal group of BBN(6-14) attached to an Aoc spacer; the Ki value of DOTA-Aoc-BBN(6-14) monomer being similar. Variable NPY1R affinities, Ki=4.5 to 45 µM, were obtained with this peptide heterodimer arrangement when DOTA was apart of the molecule. A very good NPY1R affinity (Ki=67 nM) was obtained with (DOTA)Lys4BVD-15, the monomer.

Conclusions: We propose a new class of radiopharmaceuticals, peptide heterodimers, to improve breast and prostate cancer diagnosis by PET. In vitro binding studies confirmed that dual-receptor targeting was feasible and possible but the design can be improved.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Guérin, B. Articles by Bénard, F. PubMed Articles by Guérin, B. Articles by Bénard, F.