title: Development of a new radioligand for cholecystokinin receptor subtype 2 scintigraphy: from molecular modeling to in vivo evaluation.
abstract: To improve the targeting to tumors expressing the cholecystokinin receptor subtype 2 (CCK2R) with limited kidney uptake, we synthesized a novel cholecystokinin C-terminal tetrapeptide (CCK4)-based derivative conjugated to an original bipyridine-chelator (BPCA), 111In-BPCA-(Ahx)2-CCK4. To our knowledge this is the first CCK4-based radioligand that presents a high affinity for the CCK2R, a high and specific tumor uptake, a low renal accumulation and a very good visualization of tumors in vivo compared with an internal control, 111Indium-trans-cyclohexyldiethylenetriaminepenta-acetic acid-cholecystokinin octapeptide (111In-CHX-A''-DTPA-CCK8). These properties make 111In-BPCA-(Ahx)2-CCK4, a promising candidate for imaging and peptide receptor radionuclide therapy of CCK2R positive tumors.
authors.affiliation: INSERM 563, Equipe Marc Poirot, CPTP, Département d'Imagerie Médicale, Institut Claudius Regaud, Toulouse, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Brillouet
authors.forename: Sandra
authors.initials: S
authors.lastname: Dorbes
authors.forename: Frédéric
authors.initials: F
authors.lastname: Courbon
authors.forename: Claude
authors.initials: C
authors.lastname: Picard
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Delord
authors.forename: Eric
authors.initials: E
authors.lastname: Benoist
authors.forename: Marc
authors.initials: M
authors.lastname: Poirot
authors.forename: Béatrice
authors.initials: B
authors.lastname: Mestre-Voegtlé
authors.forename: Sandrine
authors.initials: S
authors.lastname: Silvente-Poirot
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000000981:diagnostic imaging*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004369:Pentetic Acid / Q000031:analogs & derivatives; D011877:Radionuclide Imaging / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D043887:Receptor, Cholecystokinin B / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; D019275:Radiopharmaceuticals; D043887:Receptor, Cholecystokinin B; D004369:Pentetic Acid