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The purpose of this study was to quantify D2 receptors density and affinity in living rats using [11C]raclopride and to validate the multiinjection modelling approach. To this aim, we used an intracerebral β+-sensitive probe as a highly sensitive system to quantify the radioligand activity using a single three-injection experimental paradigm. The study was divided into three main parts: (i) [11C]raclopride catabolism evaluation without and with cimetidine pretreatment (cytochrome P450 inhibitor); (ii) quantification of kinetics parameters in the striatum, enthorinal cortex, and cerebellum of living rats using a three-compartment model with an arterial input function; (iii) correlation study of in vivo and in vitro binding density and affinity values in the same striatal tissues. (i) raclopride catabolism was very reproducible between individuals; cimetidine pre-treatment resulted in a 30% reduction of raclopride metabolites. (ii) D2 striatal B′max and KdVr estimates obtained by compartmental modelling were 19.87±6.45 and 6.2±3.3 nmol/L, respectively. Cerebellum is the best candidate as a reference region with no specific binding detectable in vivo. (iii) When comparing density (Bmax/B′max) and affinity (Kd/KdVr) values in vivo and in vitro for each striatum, a high strict correlation was found (r2=0.90 and 0.72, for density and affinity, respectively). These results validate the multi-injection modelling approach coupled to β-microprobe acquisitions as a mean to provide accurate and separate estimates of dopamine D2-receptor density and affinity, in the living rodent striatum.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 1517–1527. doi:10.1038/sj.jcbfm.9600141; published online 25 May 2005 [ABSTRACT FROM AUTHOR]