title: A high-affinity near-infrared fluorescent probe to target bombesin receptors.
abstract: OBJECTIVE
  This study aimed to create new optical surgical navigation NIRF probes for prostate and breast cancers.
  
  
  METHODS
  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.
authors.affiliation: Department of Radiology, The Ohio State University, Columbus, OH, 43210, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Shrivastava
authors.forename: Haiming
authors.initials: H
authors.lastname: Ding
authors.forename: Shankaran
authors.initials: S
authors.lastname: Kothandaraman
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.forename: Michelle
authors.initials: M
authors.lastname: Williams
authors.forename: Keisha
authors.initials: K
authors.lastname: Milum
authors.forename: Song
authors.initials: S
authors.lastname: Zhang
authors.forename: Michael F
authors.initials: MF
authors.lastname: Tweedle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001839:Bombesin / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D018004:Receptors, Bombesin / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; D018004:Receptors, Bombesin; D001839:Bombesin