A High-Affinity Near-Infrared Fluorescent Probe to Target Bombesin Receptors

• Published in: Molecular imaging and biology Vol. 16; no. 5; pp. 661 - 669
• Main Authors: Shrivastava, Ajay, Ding, Haiming, Kothandaraman, Shankaran, Wang, Shu-Huei, Gong, Li, Williams, Michelle, Milum, Keisha, Zhang, Song, Tweedle, Michael F.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.10.2014; Springer Nature B.V
• Subjects: Amino Acid Sequence; Animals; Bombesin - chemistry; Bombesin - metabolism; Cell Line, Tumor; Female; Fluorescent Dyes - chemistry; Fluorescent Dyes - pharmacokinetics; Humans; Imaging; Inhibitory Concentration 50; Medicine; Medicine & Public Health; Mice, Inbred BALB C; Mice, Nude; Molecular Sequence Data; Protein Binding; Radiology; Rats; Receptors, Bombesin - metabolism; Research Article; Spectroscopy, Near-Infrared - methods; Xenograft Model Antitumor Assays; Bombesin; AMBA; Optical; NIRF; IR800CW; Gastrin-releasing peptide; Surgical navigation; Near-infrared fluorescent
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-014-0727-2

Purpose This study aimed to create new optical surgical navigation NIRF probes for prostate and breast cancers. Procedures IR800-linker-QWAVGHLM-NH 2 with linker = GSG, GGG, and G-Abz4 were synthesized and characterized. IC 50 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 IC 50 (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.