title: In vivo evaluation of new carfentanil-based radioligands for the mu opiate receptor.
abstract: Eight derivatives of [(11)C]carfentanil were evaluated as alternative mu opioid receptor radioligands with the potential for lower pharmacological activity, faster pharmacokinetics, and/or lower non-specific binding. Derivatives with aryl ring substituents or alkyl group substitutions were prepared in carbon-11 labeled form and examined for initial brain uptake and regional brain tissue pharmacokinetics in mouse brain. Promising derivatives with chloro, methoxy and methyl substituents on one aryl ring were then evaluated for specific binding in an equilibrium infusion rat model of regional brain distributions. Although no derivatives were identified with improved pharmacokinetics or lower non-specific binding, several derivatives show acceptable in vivo specific binding properties and may deserve further evaluation as less potent and thus safer compounds for in vivo imaging studies.
authors.affiliation: Division of Nuclear Medicine, Department of Radiology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Jewett
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kilbourn
mesh_terms: D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics*; D007700:Kinetics; D008024:Ligands; D051379:Mice; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D017450:Receptors, Opioid, mu; C017114:carfentanil; D005283:Fentanyl