Noninvasive Nuclear Imaging Enables the In Vivo Quantification of Striatal Dopamine Receptor Expression and Raclopride Affinity in Mice

¹¹C-raclopride PET/MR images of mouse brain corresponding to time–activity curves (Fig. 1B) using BI protocol. Mice were scanned with decreasing SA: high SA, medium SA, low SA, and very low SA. PET images averaged over all time frames after ¹¹C-raclopride injection are shown. PET images clearly depict large decrease in ¹¹C-raclopride binding in striatal regions with increasing raclopride mass. Volumes of interest of striatum and cerebellum are inserted in left image to demonstrate lack of spillover from Harderian glands. CER = cerebellum; HG = Harderian glands; Max = maximum; Min = minimum; STR = striatum.

(A) Dose–response curve: BP_ND calculated from Logan graphical analysis was plotted as function of raclopride dose in nmol/kg of body weight. Graph clearly shows that raclopride dose of 4 nmol/kg or more decreases BP_ND estimates. (B) Occupancy plots as function of raclopride dose (nmol/kg). Injected raclopride dose of 4.5 nmol/kg (1.7 μg/kg) yielded approximately 10% receptor occupancy, corresponding to SA value of 100 GBq/μmol.

Quantification of ¹¹C-raclopride PET data assuming single-binding-site model. Data were generated from BCI (n = 7) (A) and BI (n = 12) (B) experiments using decreasing SA for each mouse. To determine appB_max and appK_d, BP_ND values were plotted against free tracer concentration (F), which was estimated from cerebellum. Nonlinear regression analysis was applied to data, and best fits were obtained when nonsaturable binding was included in fit (solid line = NSAT term, dotted line = without NSAT term). Ratio of bound to free ¹¹C-raclopride concentration (B/F) was plotted as function of bound ¹¹C-raclopride concentration (B) using Scatchard analysis. Plots from BCI (C) and BI (D) experiments did not show linear relationship. Linear regression lines from 2-, 3-, and 4-point Scatchard plots are shown as insets. x-intercept and slope were used to calculate appB_max and appK_d. Values are shown in Supplemental Table 4.