Impact of Isoflurane Anesthesia on D2 Receptor Occupancy by 18Ffallypride Measured by MicroPET With a Modified Logan Plot

摘要

In the previous work, we reported a method that utilized imaging data collected from 60 to 120 min following [¹⁸F]fallypride administration to estimate the distribution volume ratio DVR′ (DVR′ ∝ 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 [¹⁸F]fallypride DVR′.MethodsRats were injected with [¹⁸F]fallypride either unconsciously under ~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 [¹⁸F]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 [¹⁸F]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 k3/k4 (≈ BPND) for the 60 and 120 min acquisitions.