Reproducibility of repeated measures of cholinergic terminal density using[F-18](+)-4-fluorobenzyltrozamicol and PET in the rhesus monkey brain

[F-18](+)-4-fluorobenzyltrozamicol (FBT), which selectively binds to the ve sicular acetylcholine transporter in the presynaptic cholinergic neuron, ha s previously been shown to be a useful ligand for the study of cholinergic terminal density in the basal ganglia with PET. The goal of this study was to assess the test-retest variability of [F-18]FBT and PET measurements und er baseline conditions in the basal ganglia. Methods: After approval from t he Animal Care and Use Committee, 6 rhesus monkeys underwent a series of 2 [F-18]FBT PET scans (time between scans, 32-301 d) under isoflurane anesthe sia. Each scan was initiated on the bolus injection of the radiotracer and consisted of 26 frames acquired during 180 min. Arterial blood samples were collected over the course of each scan to determine the metabolite-correct ed arterial input function. Tissue time-activity curves were obtained from the scan data by drawing regions of interest over the basal ganglia and cer ebellum. The distribution volume ratio for the basal ganglia was then deter mined for each scan by taking the ratio of the basal ganglia (specific bind ing) to cerebellum (nonspecific binding) distribution volume. Distribution volumes were derived using the Logan graphic analysis technique as well as a standard 3-compartment model. Additionally, the radioactivity concentrati on ratio was calculated as the ratio of the average [F-18]FBT concentration in the basal ganglia to that in the cerebellum during the last half of the study (85-170 min), The constant K-1, determined using the standard 3-comp artment model, was used as an index of blood flow changes between studies. Results: For all subjects, the test-retest variability was less than 15% fo r the distribution volume ratio and 12% for the radioactivity concentration ratio. Good agreement was found between the distribution volume ratio calc ulated using the graphic technique and the standard 3-compartment model. Us ing K-1 as an index, the variability in blood flow seen in both the basal g anglia and the cerebellum was significantly reduced in their ratio. Conclus ion: These results show the reproducibility of [F-18]FBT and PET measuremen ts in the basal ganglia.