Awake Nonhuman Primate Brain PET Imaging with Minimal Head Restraint: Evaluation of GABAA Benzodiazepine Binding with 11CFlumazenil in Awake and Anesthetized Animals

摘要

Neuroreceptor imaging in the nonhuman primate (NHP) is valuable for translational research approaches in humans. However, the majority of NHP studies are conducted under anesthesia, which affects the interpretability of receptor binding measures. The aims of this study are to develop awake NHP imaging with minimal head restraint and to compare in vivo binding of GABAA-benzodiazepine radiotracer [¹¹C]flumazenil under anesthetized and awake conditions. We hypothesized that [¹¹C]flumazenil binding potential (BPND) would be higher in isoflurane-anesthetized monkeys.MethodsThe Focus-220 small animal PET scanner was fitted to a mechanical device that raised and tilted the scanner 45° while the awake NHP was tilted back 35° in a custom chair for optimal brain positioning. This required acclimation of the animals to the chair, touch-screen tasks, i.v. catheter insertion, and tilting. For PET studies, the bolus plus constant infusion (B/I) method was used for [¹¹C]flumazenil administration. Two rhesus monkeys were scanned under the awake (n=6 scans) and isoflurane-anesthetized (n=4 scans) conditions. The Vicra infrared camera was used to track head motion during PET scans. Under the awake condition, emission and head motion-tracking data were acquired for 40-75 min post-injection. Anesthetized monkeys were scanned for 90 min. Cortisol measurements were acquired during awake and anesthetized scans. Equilibrium analysis was used for both the anesthetized (n=4) and awake (n=5) datasets to compute mean BPND images in NHP template space, using the pons as a reference region. Percent change per min (%Δ/min) in radioactivity concentration was calculated in high and low binding regions to assess the quality of equilibrium.