title: Synthesis and evaluation of a fluorescent non-peptidic cholecystokinin-B/gastrin receptor specific antagonist for cancer cell imaging.
abstract: Fluorescent labeling has enabled a better understanding of the relationships between receptor location, function, and life cycle. Each of these perspectives contributes new insights into drug action, particularly for G protein-coupled receptors (GPCRs). The aim of this study was to develop a fluorescein derivative, FLUO-QUIN-a novel antagonist of the cholecystokinin-B/gastrin receptor. A radioligand-binding experiment revealed an IC(50)  of 4.79 nm, and the antagonist inhibited gastric acid secretion in an isolated lumen-perfused mouse stomach assay (up to 51 % at 100 nm). The fluorescence properties altered upon binding to the receptor, and the fluorophore was quenched to a greater extent when free than in the bound form. FLUO-QUIN specifically bound to human pancreatic carcinoma cells, MiaPaca-2, which are known to express the receptor, as evidenced by rapid clustering followed by time-dependent receptor internalization. This proves the stability of FLUO-QUIN and its ability to penetrate vesicular membranes and reach various cell targets. Hence it might be used as an agent for the detection of CCK-B-receptor-positive tumors by fluorescence imaging.
authors.affiliation: Dr. BR Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Saroj
authors.initials: S
authors.lastname: Kumari
authors.forename: Joyita
authors.initials: J
authors.lastname: Chowdhury
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Sudhir
authors.initials: S
authors.lastname: Chandna
authors.forename: Daman
authors.initials: D
authors.lastname: Saluja
authors.forename: Madhu
authors.initials: M
authors.lastname: Chopra
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002477:Cells / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D005452:Fluoresceins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005456:Fluorescent Dyes; D006727:Hormone Antagonists / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000175:diagnosis*; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D001570:Benzodiazepinones; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006727:Hormone Antagonists; D011799:Quinazolines; D043887:Receptor, Cholecystokinin B; D013890:Thiourea; C046367:asperlicin