title: Fluorine-18-labeled benzamide analogues for imaging the sigma2 receptor status of solid tumors with positron emission tomography.
abstract: A series of fluorine-containing benzamide analogs was synthesized and evaluated as candidate ligands for positron emission tomography (PET) imaging of the sigma-2 (sigma2) receptor status of solid tumors. Four compounds having a moderate to high affinity for sigma2 receptors and a moderate to low affinity for sigma-1 (sigma1) receptors were radiolabeled with fluorine-18 via displacement of the corresponding mesylate precursor with [18F]fluoride. Biodistribution studies in female Balb/c mice bearing EMT-6 tumor allografts demonstrated that all four F-18-labeled compounds had a high tumor uptake (2.5-3.7% ID/g) and acceptable tumor/normal tissue ratios at 1 and 2 h post-i.v. injection. An analysis of the chemistry and biodistribution data suggested that N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-[18F]-fluoroethoxy)-5-methylbenzamide ([18F]3c) and N-(4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)butyl)-2-(2-[18F]-fluoroethoxy)-5-iodo-3-methoxybenzamide ([18F]3f) are acceptable compounds for imaging the sigma2 receptor status of solid tumors.
authors.affiliation: Division of Radiological Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu
authors.forename: Jinbin
authors.initials: J
authors.lastname: Xu
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Jones
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.forename: Craig
authors.initials: C
authors.lastname: Dumstorff
authors.forename: Suwanna
authors.initials: S
authors.lastname: Vangveravong
authors.forename: Delphine L
authors.initials: DL
authors.lastname: Chen
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Wheeler
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006168:Guinea Pigs; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D017480:Receptors, sigma / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D001549:Benzamides; D005462:Fluorine Radioisotopes; D017480:Receptors, sigma