A high-affinity near-infrared fluorescent probe to target bombesin receptors.

ABSTRACT: PURPOSE:This study aimed to create new optical surgical navigation NIRF probes for prostate and breast cancers. PROCEDURES:IR800-linker-QWAVGHLM-NH2 with linker = GSG, GGG, and G-Abz4 were synthesized and characterized. IC50 for bombesin receptors (BBN-R) in PC-3 prostate and T47D breast cancer cells, fluorescence microscopy in PC-3 cells, and NIRF imaging in mice PC-3 tumor xenografts were studied. RESULTS:GGG, GSG, and G-Abz4 derivatives had IC50 (nM) for BBN-R+ PC-3 cells?=?187?±?31, 56?±?5, and 2.6?±?0.2 and T47D cells?=?383?±?1, 57.4?±?1.2, and 3.1?±?1.1, respectively. By microscopy the Abz4 derivative showed the highest uptake, was competed with by BBN, and had little to no binding to BBN-R- cells. In NIRF imaging the G-Abz4 probe was brighter than GGG probe in BBN-R+ tissues in vivo and tissues, tumors, and tumor slices ex vivo. Uptake could be partially blocked in BBN-R+ pancreas but not visibly in tumor. CONCLUSIONS:Linker choice can dominate peptidic BBN-R binding. The G-Abz4 linker yields a higher affinity and specific BBN-R binder in this series of molecules.

SUBMITTER: Shrivastava A 

PROVIDER: S-EPMC5885141 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature