In vivo comparative imaging of dopamine D2 knockout and wild-type mice with (11)C-raclopride and microPET

Abstract

The use of mice with targeted gene deletions (knockouts [KOs]) provides an important tool to investigate the mechanisms underlying behavior, neuronal development, and the sequella of neuropsychiatric diseases. MRI has been used to image brain structural changes in KO mice but, to our knowledge, the feasibility of using PET to investigate brain neurochemistry in KO mice has not been demonstrated.

Methods: We have evaluated the sensitivity of the microPET to image dopamine D2 receptor (DRD2) KO mice (D2-/-). PET measurements were performed in wild-type (D2+/+) mice and KO (D2-/-) mice using a microPET scanner. Briefly, each animal was anesthetized and injected intravenously with (11)C-raclopride, a DRD2-specific ligand, and dynamic PET scanning was performed for 60 min.

Results: The (11)C-raclopride images of the KO mice showed significantly lower binding in the striatum (ST) than those of the wild-type (WT) mice, which was confirmed by the time-activity curves that revealed equivalent binding in the ST and cerebellum (CB) in KO mice, whereas the WT mice had significantly higher binding in the ST than in the CB. The ST/CB ratio was significantly higher in WT mice than in KO mice (ST/CB = 1.33 +/- 0.13 and 1.05 +/- 0.03, respectively; P < 0.002; n = 10). The microPET images were compared qualitatively with conventional autoradiography images.

Conclusion: These data support the use of microPET as an effective in vivo imaging tool for studying noninvasively KO mice. These same tools can be extended to investigate other genetically engineered murine models of disease. Future studies will seek to use microPET to investigate the relationships between genes, neuronal activity, and behavior.