Quantification of delta-opioid receptors in human brain with N1 '-([C-11]methyl) naltrindole and positron emission tomography

The regional binding of N1'-([C-11]methyl)naltrindole (MeNTI), a selective delta-opioid antagonist, was studied in healthy human subjects with positro n emission tomography (PET). After the bolus intravenous administration of high specific activity [C-11]MeNTI, PET was performed over 90 minutes. Arte rial plasma samples were obtained during the scanning period and assayed fo r the presence of radiolabeled metabolites. The data were analyzed with var ious kinetic (two and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scan ning time) approaches. This tracer showed irreversible binding characterist ics during the scanning period used. The results of the analyses also were compared with the density and distribution of delta-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport cha nges on the perceived binding parameters obtained with the models. A constr ained three-compartment kinetic model was demonstrated to be superior to ot her quantification models for the description of MeNTI kinetics and quantif ication of delta receptor binding in the human brain with C-11-labeled MeNT I.