Quantitative analysis of (-)-N-11C-propyl-norapomorphine in vivo binding in nonhuman primates

(-)-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 (V₃″) 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. V₃″ values derived with SRTM were well correlated with but slightly higher than V₃″ values derived with kinetic analysis. Using any method, a significant difference was detected in BP and V₃″ values between the 2 animals. It was determined that 30 min of scanning data were sufficient to derive V₃″ 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.