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This is a particularly important consideration in the context of in vivo competition studies, where a pharmacological challenge can be administered during the interval of steady\u2010state ligand binding, as in the case of [<jats:sup>11<\/jats:sup>C]\u2010raclopride studies with amphetamine challenge. However, the short half\u2010life of <jats:sup>11<\/jats:sup>C imposes limits on the practical duration of constant infusions. Therefore, we chose to test [<jats:sup>18<\/jats:sup>F]\u2010DMFP as a tracer for dopamine D<jats:sub>2\/3<\/jats:sub> receptors in rat striatum in the paradigm. Using a conventional bolus injection, the [<jats:sup>18<\/jats:sup>F]\u2010DMFP BP<jats:sub>ND<\/jats:sub> was 3.8 in striatum of anesthetized rats. When followed by a constant infusion, we obtained quasi\u2010stable BP<jats:sub>ND<\/jats:sub> estimates of 4.5 within an interval of 45 min. During infusions lasting up to 4 h, BP<jats:sub>ND<\/jats:sub> declined progressively. This seemed due to the progressive spill\u2010in of radioactivity from the cranium to the cerebellum reference region, despite optimized iterative reconstruction of the images. Therefore, we propose a new concept of compensation for this spill\u2010in effect using pharmacokinetic considerations, without requiring high\u2010resolution anatomical images. Challenge with amphetamine (1 and 4 mg\/kg) evoked an \u223c25% reduction in BP<jats:sub>ND<\/jats:sub>. There was no clear evidence of dose\u2010dependence in the striatal\u2010binding changes, despite the considerably greater physiological effect, as documented by ECG. Thus, the general applicability of the bolus plus infusion method with [<jats:sup>18<\/jats:sup>F]\u2010DMFP for small animal studies is impeded by the substantial labeling of the cranium. The cranial uptake was linear, indicating first\u2010order kinetics for the enzymatic defluorination of the tracer. Based on this phenomenon, we developed an analytic method compensating for the effects of progressive cranial labeling on the estimation of specific binding in striatum. 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