Gastrin−releasing peptide (GRP) receptors are overexpressed on a variety of human carcinomas, including those of the breast. These receptors may be targeted with bombesin (BBN), which binds to GRP receptors with high affinity and specificity. The aim of this study was to develop a (99m)Tc(I)−BBN analog with favorable pharmacokinetic properties in order to improve the visualization of breast cancer tissue.

Solid−phase peptide synthesis was used to produce a series of X−Y−BBN−NH2 conjugates, where X is pyrazolyl (PZ1) or 2,3−diaminopropionic acid (DPR) and Y is a spacer sequence. Their metallated counterparts were prepared by reacting [(99m)Tc−(H(2)O)(3)(CO)(3)](+) with the corresponding ligand.

While the PZ1 conjugates exhibited higher GRP receptor binding affinities in vitro, the DPR analogs demonstrated superior target tissue accumulation and pharmacokinetic properties in vivo.

These results demonstrate the ability of the DPR derivatives (Y=glycylserylglycine, triserine) to clearly identify the T47−D tumor tissue in xenografted SCID mice.

PMID: 20150613 [PubMed − indexed for MEDLINE] Source: National Library of Medicine.