Quantitative Analysis of (a?’)-N-11C-Propyl-Norapomorphine In Vivo Binding in Nonhuman Primates

摘要

id="p-1">(a?’)-N-11C-propyl-norapomorphine (11C-NPA) is a new dopamine agonist PET radiotracer that holds potential for imaging the high-affinity states of dopamine D₂-like receptors in the living brain. The goal of this study was to develop and evaluate analytic strategies to derive in vivo 11C-NPA binding parameters. >Methods: Two baboons were scanned 4 times after 11C-NPA injections. The metabolite-corrected arterial input functions were measured. Regional brain time-activity curves were analyzed with kinetic and graphical analyses, using the arterial time-activity curve as the input function. Data were also analyzed with the simplified reference-tissue model (SRTM) and graphical analysis with reference-region input. >Results: 11C-NPA exhibited moderately fast metabolism, with 31% ?± 5% of arterial plasma concentration corresponding to the parent compound at 40 min after injection. Plasma clearance was 29 ?± 1 L/h, and plasma free fraction (f₁) was 5% ?± 1%. For kinetic analysis, a 1-tissue compartment model (1TCM) provided a good fit to the data and more robust derivations of the tissue distribution volumes (V_T, in mL/g) than a 2-tissue compartment model (2TCM). Using 1TCM, V_Ts in the cerebellum and striatum were 3.4 ?± 0.4 and 7.5 ?± 2 mL/g, respectively, which led to estimates of striatal binding potential (BP) of 4.0 ?± 1.1 mL/g and striatal equilibrium specific-to-nonspecific partition coefficient (V₃a€3) of 1.2 ?± 0.2. V_T values derived with graphical analysis were well correlated with but slightly lower than V_T values derived with kinetic analysis. V₃a€3 values derived with SRTM were well correlated with but slightly higher than V₃a€3 values derived with kinetic analysis. Using any method, a significant difference was detected in BP and V₃a€3 values between the 2 animals. It was determined that 30 min of scanning data were sufficient to derive V₃a€3 values using kinetic, graphical (arterial input and reference-region input), and SRTM analyses. >Conclusion: This study indicates that 11C-NPA is a suitable PET tracer to quantify the agonist high-affinity sites of D₂-like receptors.