¹¹C-preladenant is a selective antagonist for mapping of cerebral adenosine A_2A receptors (A_2ARs) by PET. This is a first-in-human study to examine the safety, radiation dosimetry, and brain imaging of ¹¹C-preladenant in healthy human subjects. Methods: Dynamic ¹¹C-preladenant PET scans (90 min) were obtained in 5 healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined. For anatomic coregistration, T1-weighted MRI was performed. The total distribution volume (V_T) was estimated using 1- and 2-tissue-compartment models (1T and 2T, respectively). The distribution volume ratio (DVR) was calculated from V_T of target and reference region and obtained with a noninvasive Logan graphical reference tissue method (t* = 30 min). The applicability of a shortened protocol as an alternative to the 90-min PET scan was investigated. Tracer biodistribution and dosimetry were determined in 3 healthy male subjects, using serial whole-body PET scans acquired over 2 h after ¹¹C-preladenant injection. Results: There were no serious adverse events in any of the subjects throughout the study period. ¹¹C-preladenat readily entered the brain, with a peak uptake in the putamen and head of the caudate nucleus 30−40 min after tracer injection. Other brain regions showed rapid clearance of radioactivity. The regional distribution of ¹¹C-preladenant was consistent with known A_2AR densities in the brain. At pseudoequilibrium (reached at 40 min after injection), stable target–to–cerebellar cortex ratios of around 3.8−10.0 were obtained. The 2T fit better than the 1T in the low-density A_2AR regions. In contrast, there were no significant differences between 1T and 2T in the high-A_2AR-density regions. DVRs in the putamen and head of the caudate nucleus were around 3.8−10.3 when estimated using a Logan graphical reference tissue method with cerebellum as the reference region. PET scanning at 50 or 70 min can provide the stable DVR estimates within 10% or 5% differences at most, respectively. The radioactivity was mainly excreted through the hepatobiliary system after ¹¹C-preladenant injection. As a result, the absorbed dose (μGy/MBq) was highest in the gallbladder wall (mean ± SD, 17.0 ± 2.5) and liver (11.7 ± 2.1). The estimated effective dose for ¹¹C-preladenant was 3.7 ± 0.4 μSv/MBq. Conclusion: This initial evaluation indicated that ¹¹C-preladenat is suitable for imaging of A_2ARs in the brain.

¹¹ C-催乳剂是通过PET定位脑腺苷A _2A受体（A _2A Rs）的选择性拮抗剂。这是一项在人类中进行的首次研究，目的是检查健康人类受试者中¹¹ C促进剂的安全性，辐射剂量法和脑成像。方法：在5名健康男性受试者中进行了动态¹¹ C标记PET扫描（90分钟）。在扫描期间，以不同的时间间隔对动脉血进行采样，并确定血浆中母体化合物的比例。对于解剖融合，进行了T1加权MRI。总分配量（V _T）是使用1和2组织隔间模型（分别为1T和2T）估算的。根据目标区域和参考区域的V _T计算分布体积比（DVR），并通过非侵入式Logan图形参考组织方法获得（t * = 30分钟）。研究了缩短方案作为90分钟PET扫描的替代方法的适用性。示踪剂的生物分布和剂量测定法在3名健康男性受试者中进行了测定，使用了在注入¹¹ C的前2 h内进行的连续全身PET扫描。结果：在整个研究期间，所有受试者均未出现严重不良事件。¹¹注射示踪剂后30-40分钟，C-preladenat容易进入大脑，其壳壳和尾状核头部的摄取量达到峰值。其他大脑区域显示放射性快速清除。¹¹ C-preladenant的区域分布与大脑中已知的A _2A R密度一致。在假平衡时（注射后40分钟达到），靶标至小脑皮层的比率稳定在3.8-10.0左右。在低密度A _2A R区域中2T比1T更适合。相比之下，高A _2A的1T和2T之间没有显着差异R密度区域。当使用Logan图形参考组织方法（以小脑作为参考区域）进行估算时，壳状核和尾状核头部的DVR约为3.8-10.3。在50分钟或70分钟进行PET扫描可以分别将DVR估算值稳定在最多10％或5％之内。注入¹¹ C的放射性物质主要通过肝胆系统排泄。结果，在胆囊壁（平均值±SD，17.0±2.5）和肝脏（11.7±2.1）中吸收剂量（μGy/ MBq）最高。¹¹ C-preladenant的估计有效剂量为3.7±0.4μSv/ MBq。结论：初步评估表明¹¹ C-preladenat适用于A _2A成像大脑中的Rs。