Impact of Isoflurane Anesthesia on D2 Receptor Occupancy by [18F]fallypride Measured by MicroPET With a Modified Logan Plot

In the previous work, we reported a method that utilized imaging data collected from 60 to 120 min following [F-18] fallypride administration to estimate the distribution volume ratio DVR' (DVR' proportional to DVR; DVR = 1 + BPND, where BPND is a measure of receptor density, DA D2 in this case). In this work, we use this method to assess the effects of isoflurane anesthesia on [F-18] fallypride DVR'. Methods: Rats were injected with [F-18] fallypride either unconsciously under similar to 1.5% isoflurane via the tail vein (Group 1) or consciously via a catheter inserted either in the jugular vein (Group 2) or the tail vein (Group 3). After about 1 h of free access to food and water the rats were anesthetized with 1.5% isoflurane and imaged in a microPET for 60 min. The rats that were injected consciously (Groups 2 and 3) were placed in a rat restrainer during [F-18]fallypride injection. They were habituated in that restrainer for 3 days prior to the experiment day to minimize restraint-related stress. For comparison, a control group of rats was imaged for 120 min simultaneously with the administration of [F-18]fallypride i.v. while under 1.5% isoflurane. The DVR' estimates from the 60 min acquisitions were compared with the DVR' from the last 60 min of the 120 min acquisitions (after neglecting the first 60 min). In addition, the striatal time-activity curves were fit with a 2-tissue + plasma compartment model using an arbitrary simulated plasma input function to obtain k(3)/k(4) (approximate to BPND) for the 60 and 120 min acquisitions. Results: Isoflurane anesthesia caused a significant reduction, up to 22%, in the DVR' estimates, which were 15.7 +/- 0.3 (mean +/- SE) for the controls, 17.7 +/- 0.3 for Group 1, 19.2 +/- 0.4 for Group 2, and 18.8 +/- 0.7 for Group 3. The compartmental model fit produced similar results, similar to 30% reduction in k(3)/k(4) for the 120-min acquisitions compared with the 60-min acquisitions (initial conscious uptake of the radiotracer). Conclusion: The results of this study demonstrate that isoflurane anesthesia significantly decreases striatal [F-18] fallypride BPND in rats. Of similar importance, this work demonstrates the effectiveness of delayed scans following radiotracer injection and the implication that different types of studies can be conducted simultaneously with this method, including studies of behavioral and environmental impact on brain receptors. Synapse 65:1173-1180, 2011. (C) 2011 Wiley-Liss, Inc.