Abstract
1908
Objectives Gastrin releasing peptide receptors (GRPR) and neuropeptide Y1 receptors (NPY1R) have been shown to be highly overexpressed in a large proportion of breast cancers making these receptors prime candidates for diagnostic applications.The purpose of this study was to evaluate a novel NPY1R/GRPR binding peptide as a potential dual-action tracer for breast PET imaging, the 64Cu-(DOTA)BVD15/BBN(6-14).
Methods The branched heterodimer (DOTA)BVD15/BBN(6-14) were prepared and labelled with Cu-64. Competitive binding assays were performed on human breast cancer cell lines (T47D). Biodistribution studies were done on T47D implanted on balb/c nu/nu female mice. Plasma stability studies were achieved by incubating the 64Cu-labelled heterodimer 37 °C in fresh mouse serum for 1 h.
Results Excellent GRPR and NPY1R affinities (Ki values of 1 nM and 105 nM for GRPR and NPY1R respectively) were achieved with the branched-DOTA-heterodimer. The % i.d/g and the tumor-to-muscle ratio were 4.0±2.8 and 7.6±5.4 respectively at 1 h for the T47D tumor. Co-injection of unlabeled peptides to block receptor sites resulted in a significant reduction of the tumor uptake. HPLC analysis, after 1 h incubation in mouse plasma, showed no degradation of the radiolabelled heterodimer.
Conclusions The branched heterodimer 64Cu(DOTA)BVD15/BBN(6-14) showed promising results has high in vitro affinities for both receptors and good tumor uptake were observed in vivo. This tracer shows an excellent stability in mouse plasma.
- © 2009 by Society of Nuclear Medicine