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In Vivo Comparative Imaging of Dopamine D2 Knockout and Wild-Type Mice with ¹¹C-Raclopride and MicroPET

¹ Medical Department, Brookhaven National Laboratory, Upton, New York
² Chemistry Department, Brookhaven National Laboratory, Upton, New York
³ Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon

View larger version (129K): [in a new window]   FIGURE 1. Photograph of Concorde microPET R4 system.

View larger version (97K): [in a new window]   FIGURE 2. Transverse (A and B) and sagittal (C and D) microPET images (summed across frames 11–24) of ST injected with 11C-raclopride. (A and C) WT (D2+/+) mouse. (B and D) KO (D2-/-) mouse. HG = harderian gland.

View larger version (16K): [in a new window]   FIGURE 3. (A) ST/CB binding ratio over time (mean ± SEM). (B) Representative examples of time-activity curves of ST and CB normalized to injected dose for KO (D2-/-) mice (top) and WT (D2+/+) mice (bottom). (C) DVR plot for WT () and KO () mouse. CREFdt = reference tissue radioactivity at time t; ROI(T) = ROI radioactivity at time t; t or T = time that is midpoint of scan time.

View larger version (75K): [in a new window]   FIGURE 4. MR images of WT (A) and KO (B) mouse (sagittal plane, top left; horizontal plane, top right; coronal plane, bottom left).

View larger version (21K): [in a new window]   FIGURE 5. Representative examples of time-activity curves of ST and CB normalized to injected dose for blocking study. (A) KO (D2-/-) mouse. (B) WT (D2+/+) mouse.

View larger version (94K): [in a new window]   FIGURE 6. Autoradiograms of 3H-spiperone binding autoradiography in WT (A and C, +/+) and DRD2 KO (B and D, -/-) mice. (A and B) Total binding images in presence of 0.6 nmol/L 3H-spiperone and 40 nmol/L ketanserin. (C and D) Nonspecific binding images in presence of same concentration of tritiated ligand and ketanserin plus 5 µmol/L (+)-butaclamol. DRD2 binding signal was wiped out in most of caudate putamen (CPU) region in DRD2 KO mice (B) in comparison with WT counterpart (A). CTX = cerebral cortex; Acb = nucleus accumbens.