Alexoff David L, Vaska Paul, Marsteller Douglas, Gerasimov Timofei, Li Juan, Logan Jean, Fowler Joanna S, Taintor Nicholas B, Thanos Panayotis K, Volkow Nora D
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973-5000, USA.
J Nucl Med. 2003 May;44(5):815-22.
A new generation of commercial animal PET cameras may accelerate drug development by streamlining preclinical testing in laboratory animals. However, little information on the feasibility of using these machines for quantitative PET in small animals is available. Here we investigate the reproducibility of microPET imaging of (11)C-raclopride in the rat brain and the effects of tracer-specific activity and photon scatter correction on measures of D2 receptor (D2R) availability.
Sprague-Dawley rats (422 +/- 29 g; n = 7) were anesthetized with ketamine/xylazine and catheterized for tail vein injection of (11)C-raclopride. Each animal was positioned prone in the microPET, centering the head in the field of view. MicroPET data was collected for 60 min-starting at (11)C-raclopride injection-and binned into 24 time frames (6 x 10 s, 3 x 20 s, 8 x 60 s, 4 x 200 s, 3 x 600 s). In 3 studies, (11)C-raclopride was administered a second time in the same animal, with 2-4 h between injections. In a fourth animal, raclopride (1 mg/kg) was coinjected with (11)C-raclopride for the second injection. Three rats received a single dose of (11)C-raclopride. The range of doses for all studies was 6.11-18.54 MBq (165-501 micro Ci). The specific activity at injection was 4.07-48.1 GBq/ micro mol (0.11-1.3 Ci/ micro mol). Region-of-interest analysis was performed and the distribution volume ratio (DVR) was computed for striatum/cerebellum using sinograms uncorrected and corrected for scatter using a tail-fit method.
Test-retest results showed that the (11)C-raclopride microPET DVR was reproducible (change in DVR = -8.3% +/- 4.4%). The average DVR from 6 rats injected with high specific activity (<4 nmol/kg) was 2.43 +/- 0.19 (coefficient of variation = 8%). The DVR for the blocking study was 1.23. The DVR depended on the mass of tracer (11)C-raclopride injected for doses >1.5 nmol/kg. Scatter fractions within the rat head were approximately 25%-45% resulting in an average increase of DVR of 3.5% (range, 0%-10%) after correction.
This study shows that the (11)C-raclopride microPET-derived DVR is reproducible and suitable for studying D2R availability in the rat brain. MicroPET sensitivity was sufficient to determine reproducible DVRs from (11)C-raclopride injections of 9.25 MBq (approximately 250 micro Ci). However, the effect of tracer mass on the DVR should be considered for studies using more than approximately 1-2 nmol/kg raclopride, and scatter correction has a measurable impact on the results.
新一代商用动物正电子发射断层扫描（PET）相机可能通过简化实验动物的临床前测试来加速药物研发。然而，关于在小动物中使用这些机器进行定量PET的可行性的信息却很少。在此，我们研究了大鼠脑中（11）C-雷氯必利的微型PET成像的可重复性以及示踪剂比活度和光子散射校正对D2受体（D2R）可用性测量的影响。
将Sprague-Dawley大鼠（422±29克；n = 7）用氯胺酮/赛拉嗪麻醉，并插入导管以便经尾静脉注射（11）C-雷氯必利。每只动物俯卧于微型PET中，将头部置于视野中心。从（11）C-雷氯必利注射开始收集微型PET数据60分钟，并分为24个时间帧（6×10秒、3×20秒、8×60秒、4×200秒、3×600秒）。在3项研究中，在同一只动物中第二次给予（11）C-雷氯必利，两次注射之间间隔2 - 4小时。在第四只动物中，第二次注射时将雷氯必利（1毫克/千克）与（11）C-雷氯必利共同注射。三只大鼠接受单次剂量的（11）C-雷氯必利。所有研究的剂量范围为6.11 - 18.54兆贝可（165 - 501微居里）。注射时的比活度为4.07 - 48.1吉贝可/微摩尔（0.11 - 1.3居里/微摩尔）。进行感兴趣区分析，并使用未校正散射和使用尾部拟合方法校正散射的正弦图计算纹状体/小脑的分布体积比（DVR）。
重测结果表明，（11）C-雷氯必利微型PET DVR具有可重复性（DVR变化 = -8.3%±4.4%）。6只注射高比活度（<4纳摩尔/千克）的大鼠的平均DVR为2.43±0.19（变异系数 = 8%）。阻断研究的DVR为1.23。对于剂量>1.5纳摩尔/千克，DVR取决于注射的示踪剂（11）C-雷氯必利的质量。大鼠头部内的散射分数约为25% - 45%，校正后DVR平均增加3.5%（范围为0% - 10%）。
本研究表明，（11）C-雷氯必利微型PET衍生的DVR具有可重复性，适用于研究大鼠脑中D2R的可用性。微型PET灵敏度足以从9.25兆贝可（约250微居里）的（11）C-雷氯必利注射中确定可重复的DVR。然而，对于使用超过约1 - 2纳摩尔/千克雷氯必利的研究，应考虑示踪剂质量对DVR的影响，并且散射校正对结果有可测量的影响。
