Fluorine-18-labeled benzamide analogues for imaging the sigma2 receptor status of solid tumors with positron emission tomography.
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.
Tu
Zhude
Z
Division of Radiological Sciences, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Xu
Jinbin
J
Jones
Lynne A
LA
Li
Shihong
S
Dumstorff
Craig
C
Vangveravong
Suwanna
S
Chen
Delphine L
DL
Wheeler
Kenneth T
KT
Welch
Michael J
MJ
Mach
Robert H
RH
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
D001549:Benzamides; D005462:Fluorine Radioisotopes; D017480:Receptors, sigma