Measurement of striatal and thalamic dopamine D2 receptor binding with 11C-raclopride

C-11-Raclopride is a widely used positron emission tomography (PET) tracer for measurement of striatal D-2 dopamine receptor binding characteristics. Recently, C-11-raclopride has also been used for quantification of thalamic D-2 receptor binding. We studied reproducibility and validity issues on the thalamic D-2 binding measurements using healthy volunteer test-retest data and simulated data. Eight healthy male volunteers received C-11-raclopride as a bolus injection in a standard test-retest design using 3-dimensional PET. The displacement of thalamic C-11-raclopride binding by the D-2 receptor antagonist haloperidol was studied in two female schizophrenic patients. With regards to reproducibility and reliability, thalamic C-11-raclopride binding could be described with a simplified reference tissue model resulting in binding potentials (BPs) between 0.38 and 0.66. In comparison, the model failed to describe C-11-raclopride binding consistently in temporal cortex due to low specific signal. Measurement of thalamic C-11-raclopride BP was reproducible with a test-retest variability of 7.6 +/- 6.2% and reliable with an intraclass correlation coefficient (ICC) of 0.87. Comparable ICCs were observed in caudate and putamen (0.84-0.96). With regard to validity, subchronic low dose haloperidol treatment reduced specific C-11-raclopride binding equally in putamen and thalamus but a higher dose induced clearly higher D-2 receptor occupancy in putamen than in thalamus. Noise simulations indicated that this can partly be explained by an over-estimation of thalamic D-2 receptor BP in noisy conditions (low signal, high occupancy). The D-2 receptor BP in putamen was clearly more resistant to noise. We conclude that the reproducibility and reliability of thalamic C-11-raclopride BP is good and equal to, or only slightly less than, those observed in caudate or putamen. However, the signal-to-noise ratio for quantification may become too low especially in receptor occupancy-type studies, leading to an artefactual underestimation of measured D-2 receptor occupancy. (C) 2003 Lippincott Williams Wilkins.