Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Synapse. 2011 Nov;65(11):1173-80. doi: 10.1002/syn.20955. Epub 2011 Jun 17.
In the previous work, we reported a method that utilized imaging data collected from 60 to 120 min following [(18) F]fallypride administration to estimate the distribution volume ratio DVR' (DVR' ∝ DVR; DVR = 1 + BP(ND) , where BP(ND) 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 [(18) F]fallypride DVR'.
Rats were injected with [(18) F]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 [(18) F]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 [(18) F]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) (≈ BP(ND) ) for the 60 and 120 min acquisitions.
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, ∼30% reduction in k(3) /k(4) for the 120-min acquisitions compared with the 60-min acquisitions (initial conscious uptake of the radiotracer).
The results of this study demonstrate that isoflurane anesthesia significantly decreases striatal [(18) F]fallypride BP(ND) 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.
在之前的工作中，我们报告了一种利用在 [(18) F]fallypride 给药后 60 至 120 分钟采集的成像数据来估计分布容积比 DVR'（DVR'∝DVR；DVR=1+BP(ND)，其中 BP(ND)是受体密度的度量，在这种情况下是 DA D2）的方法。在这项工作中，我们使用该方法来评估异氟烷麻醉对 [(18) F]fallypride DVR'的影响。
大鼠通过尾静脉在无意识状态下（约 1.5%异氟烷下的组 1）或通过插入颈静脉（组 2）或尾静脉（组 3）的导管在有意识状态下注射 [(18) F]fallypride。在自由进食和饮水约 1 小时后，大鼠在 microPET 中以 1.5%异氟烷麻醉并进行 60 分钟成像。在 [(18) F]fallypride 注射期间，有意识注射的大鼠（组 2 和组 3）被放置在大鼠固定器中。在实验日之前，他们在该固定器中适应了 3 天，以最大程度地减少与约束相关的压力。为了进行比较，同时在 1.5%异氟烷下静脉注射 [(18) F]fallypride 的情况下，对一组大鼠进行了 120 分钟的成像。比较了 60 分钟采集的 DVR'估计值与 120 分钟采集的最后 60 分钟的 DVR'（忽略最初的 60 分钟）。此外，使用任意模拟的血浆输入函数拟合纹状体的时间-活性曲线，以获得 60 和 120 分钟采集的 k(3)/k(4)（≈BP(ND)）。
异氟烷麻醉导致 DVR'估计值显著降低，最高可达 22%，对照组为 15.7±0.3（均值±SE），组 1 为 17.7±0.3，组 2 为 19.2±0.4，组 3 为 18.8±0.7。房室模型拟合产生了类似的结果，与 60 分钟采集相比，120 分钟采集的 k(3)/k(4)减少了约 30%（初始放射性示踪剂的有意识摄取）。
本研究结果表明，异氟烷麻醉显著降低了大鼠纹状体中 [(18) F]fallypride 的 BP(ND)。同样重要的是，这项工作证明了在放射性示踪剂注射后进行延迟扫描的有效性，以及该方法可同时进行不同类型的研究，包括对大脑受体的行为和环境影响的研究。
