Sakata Muneyuki, Ishibashi Kenji, Imai Masamichi, Wagatsuma Kei, Ishii Kenji, Hatano Kentaro, Ishiwata Kiichi, Toyohara Jun
Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, 173-0015, Tokyo, Japan.
Department of Radiology, Toranomon Hospital, Tokyo, Japan.
EJNMMI Res. 2017 Dec;7(1):26. doi: 10.1186/s13550-017-0271-6. Epub 2017 Mar 23.
N,N-di-n-propyl-2-[2-(4-[C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([C]CB184) is a novel selective radioligand for the 18-kD translocator protein (TSPO), which is upregulated in activated microglia in the brain, and may be useful in positron emission tomography (PET). We examined the safety, radiation dosimetry, and initial brain imaging with [C]CB184 in healthy human volunteers.
Dynamic [C]CB184 PET scans (90 min) were performed in five 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 with high-performance liquid chromatography. No serious adverse events occurred in any of the subjects throughout the study period. [C]CB184 was metabolized in the periphery: 36.7% ± 5.7% of the radioactivity in plasma was detected as the unchanged form after 60 min. The total distribution volume (V ) was estimated with a two-tissue compartment model. The V of [C]CB184 was highest in the thalamus (5.1 ± 0.4), followed by the cerebellar cortex (4.4 ± 0.2), and others. Although regional differences were small, the observed [C]CB184 binding pattern was consistent with the TSPO distribution in the normal human brain. Radiation dosimetry was determined in three healthy male subjects using a serial whole-body PET scan acquired over 2 h after [C]CB184 injection. [C]CB184 PET demonstrated high uptake in the gallbladder at a later time (>60 min). In urine obtained approximately 100 min post-injection, 0.3% of the total injected radioactivity was recovered, indicating hepatobiliary excretion of radioactivity. The absorbed dose (μGy/MBq) was highest in the kidneys (21.0 ± 0.5) followed by the lungs (16.8 ± 2.7), spleen (16.6 ± 6.6), and pancreas (16.5 ± 2.2). The estimated effective dose for [C]CB184 was 5.9 ± 0.6 μSv/MBq.
This initial evaluation indicated that [C]CB184 is feasible for imaging of TSPO in the brain.
N,N-二正丙基-2-[2-(4-[C]甲氧基苯基)-6,8-二氯咪唑并[1,2-a]吡啶-3-基]乙酰胺（[C]CB184）是一种新型的针对18-kD转位蛋白（TSPO）的选择性放射性配体，该蛋白在大脑中活化的小胶质细胞中上调，可能在正电子发射断层扫描（PET）中有用。我们在健康人类志愿者中研究了[C]CB184的安全性、辐射剂量学及初始脑成像。
对5名健康男性受试者进行了动态[C]CB184 PET扫描（90分钟）。扫描期间，在不同时间间隔采集动脉血，并用高效液相色谱法测定血浆中母体化合物的比例。在整个研究期间，所有受试者均未发生严重不良事件。[C]CB184在体外周被代谢：60分钟后，血浆中36.7%±5.7%的放射性被检测为未变化形式。用双组织室模型估计总分布容积（V）。[C]CB184的V在丘脑中最高（5.1±0.4），其次是小脑皮质（4.4±0.2）等。尽管区域差异较小，但观察到的[C]CB184结合模式与正常人类大脑中的TSPO分布一致。在3名健康男性受试者中，在注射[C]CB184后2小时内进行连续全身PET扫描以确定辐射剂量学。[C]CB184 PET在后期（>60分钟）显示胆囊摄取高。在注射后约100分钟收集的尿液中，回收了0.3%的总注射放射性，表明放射性通过肝胆排泄。吸收剂量（μGy/MBq）在肾脏中最高（21.0±0.5），其次是肺（16.8±2.7）、脾脏（16.6±6.6）和胰腺（16.5±2.2）。[C]CB184的估计有效剂量为5.9±0.6μSv/MBq。
这一初步评估表明，[C]CB184用于大脑中TSPO成像可行。
