Quantitation of striatal and extrastriatal D-2 dopamine receptors using PET imaging of [18F]fallypride in nonhuman primates

[18F]Fallypride is a highly selective, high-affinity dopamine D-2 receptor ligand. The high affinity, KD = 30 pM, makes it a suitable candidate for visualizing both striatal and extrastriatal binding in the brain. In this work, dynamic PET studies of two macaque monkeys were acquired along with arterial plasma samples. Compartmental analysis and Logan plots were used to analyze the striatum, thalamus, frontal, and temporal cortices and to validate a reference region of analysis which yields a distribution volume ratio (DVR). The cerebellum was used as the reference region. The results indicate that all methods of analysis are in close agreement over all the analyzed regions in the brain. The average DVRs for the two monkeys was found to be: caudate = 26, putamen = 29, thalamus = 3.8, frontal ctx = 1.7, and temporal ctx = 1.7 on a high-resolution PET scanner. It was found that a scan time of 2 h is needed to accurately estimate the DVR for all regions of the brain. The striatal regions require the longest to linearize and are the most sensitive to variations in the average tissue-to-plasma efflux constant, k̄2. For the extrastriatal regions, the effect of the k̄2 term on DVR calculation is negligible. Repeatability measurements for all regions were found to be within 10% using the DVR parameter. Synapse 38:71–79, 2000. © 2000 Wiley-Liss, Inc.