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J Neurosci Methods. 2005 May 15;144(1):25-34. Epub 2004 Dec 8.

Development of a simultaneous PET/microdialysis method to identify the optimal dose of 11C-raclopride for small animal imaging.

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Department of Neurobiology and Behavior, State University of New York at Stony Brook, NY 11794-5230, USA.


In the field of small animal positron emission tomography (PET), the assumptions underlying human and primate kinetic models may not be sustained in rodents. That is, the threshold dose at which a pharmacologic response occurs may be lower in small animals. In order to define this relationship, we combined microPET imaging using 11C-raclopride with microdialysis measures of extracellular fluid (ECF) dopamine (DA). In addition, we performed a series of studies in which a known mass of raclopride was microinfused into one striatum prior to a high specific activity (SA) systemic injection of 11C-raclopride. This single-injection approach provided a high and low SA region of radiotracer binding in the same animal during the same scanning session. Our data demonstrate that the binding potential (BP) declines above 3.5 pmol/ml (0.35 microg), with an ED50 of 8.55+/-5.62 pmol/ml. These data also provide evidence that BP may be compromised by masses of raclopride below 2.0 pmol/ml (0.326 microg). Increases in ECF DA were produced by mass doses of raclopride over 3.9 pmol/ml (0.329 microg) with an ED50 of 8.53+/-2.48 pmol/ml. Taken together, it appears that an optimal range of raclopride mass exists between 2.0 and 3.5 pmol/ml, around which the measured BP can be compromised by system sensitivity, endogenous DA, or excessive competition with unlabeled compound.

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