Human adult and adolescent biodistribution and dosimetry of the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J
Human adult and adolescent biodistribution and dosimetry of the synaptic vesicle glycoprotein 2A radioligand 11C-UCB-J
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DOI：
10.1186/s13550-020-00670-w
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发表时间：
2020-07-14
期刊：
影响因子：
3.2
通讯作者：
Carson, Richard E.
中科院分区：
文献类型：
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作者：
Bini, Jason;Holden, Daniel;Carson, Richard E.
在成人和青少年体内量化突触密度的能力对于理解神经精神障碍是至关重要的。在这里，我们进行了全身扫描，以确定C-11-UCB-J在人体内的器官辐射剂量学。方法：对4名健康成年人注射C-11-UCB-J后进行动态全身PET扫描。手动绘制脑、心、胃、肾、肝、胰腺、脾、胆、肺、膀胱和肠道的感兴趣区(ROI)。将感兴趣区应用于动态图像，生成时间-活动曲线(TAC)。去除TAC的衰减校正，计算每个ROI的曲线下面积(AUC)。然后根据注射活度和器官体积对AUC进行归一化，以得出每个器官的放射性配基滞留时间。然后将这些时间作为输入到Olinda/exm 1.0软件中，以确定这些Olinda模型的每个器官的总辐射剂量和有效剂量：女性55 kg，男性70 kg，15岁青少年。结果：视觉评估发现肝脏、脑、胆囊、胃肠道和膀胱的摄取都很高。剂量限制器官为成年男性膀胱(0.0224 mSv/mBq)和成年女性肝脏(0.0248 mSv/mBq)，单次研究剂量限值分别为2239mSv/mBq和2017mSv/mBq。对于青少年，大肠是剂量限制器官(0.0266 mSv/mBq)，单项研究剂量限值为188mBq。结论：C-11-UCB-J在成人体内的剂量学与许多碳-11标记配体的剂量学一致。总体而言，C-11-UCB-J可以安全地用于青少年，就像在成人中一样，用于测量各种神经精神障碍和其他相关疾病的突触密度。
The ability to quantify synaptic density in vivo in human adults and adolescents is of vital importance to understanding neuropsychiatric disorders. Here, we performed whole-body scans to determine organ radiation dosimetry of C-11-UCB-J in humans.Methods: Dynamic whole-body PET scans were performed in four healthy adults after injection of C-11-UCB-J. Regions of interest (ROIs) were drawn manually for the brain, heart, stomach, kidneys, liver, pancreas, spleen, gallbladder, lungs, urinary bladder, and intestines. ROIs were applied to dynamic images to generate time-activity curves (TACs). Decay correction was removed from TACs, and the area under the curve (AUC) for each ROI was calculated. AUCs were then normalized by injected activity and organ volumes to produce radioligand residence times for each organ. These times were then used as input into the OLINDA/EXM 1.0 software to determine the total radiation dose in each organ and the effective dose for these OLINDA models: 55-kg female, 70-kg male, and 15-year-old adolescent.Results: Visual evaluation detected high uptake in the liver, brain, gallbladder, gastrointestinal tract, and urinary bladder. The dose-limiting organ was the urinary bladder for adult males (0.0224 mSv/MBq) and liver for adult females (0.0248 mSv/MBq) with single-study dose limits of 2239 MBq and 2017 MBq C-11-UCB-J, respectively. For adolescents, the large intestine was the dose-limiting organ (0.0266 mSv/MBq) with a single-study dose limit of 188 MBq.Conclusions: C-11-UCB-J dosimetry in adults is consistent with those for many carbon-11-labeled ligands. Overall, C-11-UCB-J can be used safely in adolescents, as in adults, to measure synaptic density in various neuropsychiatric and other relevant disorders.