title: Comparison of [11C]diprenorphine and [11C]carfentanil binding to opiate receptors in humans by positron emission tomography.
abstract: The kinetics and regional distribution of [11C]carfentanil, a mu-selective opiate receptor agonist, and [11C]diprenorphine, a nonselective opiate receptor antagonist, were compared using paired positron emission tomography studies in two normal volunteers. Kinetics of total radioactivity (counts/mCi/pixel) was greater for [11C]diprenorphine than [11C]carfentanil in all regions. [11C]Carfentanil binding (expressed as the total/nonspecific ratio) reached near equilibrium at approximately 40 min, whereas [11C]diprenorphine showed a linear increase until approximately 60 min. Kinetics of specific binding demonstrated significant dissociation of [11C]carfentanil from opiate receptors, whereas little dissociation of [11C]diprenorphine was observed during the 90-min scan session. Regional distributions of [11C]carfentanil and [11C]diprenorphine were qualitatively and quantitatively different: Relative to the thalamus (a region with known predominance of mu-receptors), [11C]diprenorphine displayed greater binding in the striatum and cingulate and frontal cortex compared to [11C]carfentanil, consistent with labeling of additional, non-mu sites by [11C]diprenorphine. We conclude from these studies that [11C]diprenorphine labels other opiate receptor subtypes in addition to the mu sites selectively labeled by [11C]carfentanil. The nonselective nature of diprenorphine potentially limits its usefulness in defining abnormalities of specific opiate receptor subtypes in various diseases. Development of selective tracers for the delta- and kappa-opiate receptor sites, or alternatively use of unlabeled inhibitors to differentially displace mu, delta, and kappa subtypes, will help offset these limitations.
authors.affiliation: Department of Radiology (Division of Nuclear Medicine), Johns Hopkins Medical Institutions, Baltimore, Maryland.
authors.forename: J J
authors.initials: JJ
authors.lastname: Frost
authors.forename: H S
authors.initials: HS
authors.lastname: Mayberg
authors.forename: B
authors.initials: B
authors.lastname: Sadzot
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
authors.forename: J R
authors.initials: JR
authors.lastname: Lever
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: A A
authors.initials: AA
authors.lastname: Wilson
authors.forename: H N
authors.initials: HN
authors.lastname: Wagner
authors.forename: J M
authors.initials: JM
authors.lastname: Links
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004174:Diprenorphine / Q000378:metabolism*; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008297:Male; D009019:Morphinans / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D009019:Morphinans; D011957:Receptors, Opioid; D004174:Diprenorphine; C017114:carfentanil; D005283:Fentanyl