title: Quantitation of [11C]diprenorphine cerebral kinetics in man acquired by PET using presaturation, pulse-chase and tracer-only protocols.
abstract: The quantitation of regional cerebral in vivo opioid receptor rate constants using [11C]diprenorphine and positron emission tomography (PET) using 3 types of protocol (presaturation, pulse-chase naloxone displacement and tracer-only protocols) together with measurements of regional cerebral blood flow is described in normal volunteers. Arterial blood was sampled continuously for radioactivity and was corrected for metabolites and plasma/blood partition of radioactivity to provide a continuous plasma input function. A compartmental model involving 3 tissue compartments was used to describe the regional cerebral pharmacokinetics of the tracer. The compartments comprised: (1) free plus rapidly exchanging non-specifically bound ligand, (2) specifically bound, naloxone displaceable ligand, and (3) a kinetically distinguishable non-specifically bound pool. Regional estimates of fractional rate constants relating to specific binding were obtained using naloxone in a pulse-chase design of tracer displacement. Less precise estimates of these rate constraints were obtained from single-tracer-only studies, but when binding was expressed as the tissue total volume of distribution relative to plasma there was good correlation with regional values obtained from pulse-chase studies performed in the same individuals. The application of these protocols to the measurement of indices of regional-specific opioid receptor binding in the human brain is discussed.
authors.affiliation: MRC Cyclotron Unit, Hammersmith Hospital, London, UK.
authors.forename: A K
authors.initials: AK
authors.lastname: Jones
authors.forename: V J
authors.initials: VJ
authors.lastname: Cunningham
authors.forename: S K
authors.initials: SK
authors.lastname: Ha-Kawa
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Q
authors.initials: Q
authors.lastname: Liyii
authors.forename: S K
authors.initials: SK
authors.lastname: Luthra
authors.forename: J
authors.initials: J
authors.lastname: Ashburner
authors.forename: S
authors.initials: S
authors.lastname: Osman
authors.forename: T
authors.initials: T
authors.lastname: Jones
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004174:Diprenorphine / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008875:Middle Aged; D011957:Receptors, Opioid / Q000378:metabolism; D015203:Reproducibility of Results; D012107:Research Design; D014055:Tomography, Emission-Computed
chemical_list: D002250:Carbon Radioisotopes; D011957:Receptors, Opioid; D004174:Diprenorphine