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Reproducibility of Repeated Measures of Cholinergic Terminal Density Using [¹⁸F](+)-4-Fluorobenzyltrozamicol and PET in the Rhesus Monkey Brain

Division of Radiologic Sciences and Departments of Anesthesia, Comparative Medicine, Physiology, and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and Departments of Radiology, Medicinal Chemistry, and Neurosurgery, University of Minnesota, Minneapolis, Minnesota

[¹⁸F](+)-4-fluorobenzyltrozamicol (FBT), which selectively binds to the vesicular acetylcholine transporter in the presynaptic cholinergic neuron, has 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 [¹⁸F]FBT and PET measurements under baseline conditions in the basal ganglia. Methods: After approval from the Animal Care and Use Committee, 6 rhesus monkeys underwent a series of 2 [¹⁸F]FBT PET scans (time between scans, 32–301 d) under isoflurane anesthesia. 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-corrected arterial input function. Tissue time–activity curves were obtained from the scan data by drawing regions of interest over the basal ganglia and cerebellum. The distribution volume ratio for the basal ganglia was then determined for each scan by taking the ratio of the basal ganglia (specific binding) 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 concentration ratio was calculated as the ratio of the average [¹⁸F]FBT concentration in the basal ganglia to that in the cerebellum during the last half of the study (85–170 min). The constant K₁, determined using the standard 3-compartment model, was used as an index of blood flow changes between studies. Results: For all subjects, the test–retest variability was less than 15% for the distribution volume ratio and 12% for the radioactivity concentration ratio. Good agreement was found between the distribution volume ratio calculated using the graphic technique and the standard 3-compartment model. Using K₁ as an index, the variability in blood flow seen in both the basal ganglia and the cerebellum was significantly reduced in their ratio. Conclusion: These results show the reproducibility of [¹⁸F]FBT and PET measurements in the basal ganglia.

Key Words: PET • cholinergic terminals • test–retest variability

Received Aug. 17, 1999; revision accepted May 25, 2000.

For correspondence or reprints contact: H. Donald Gage, PhD, Division of Radiologic Sciences, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1061.

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