Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [18F]UCB-H: First-in-Human Study
Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [18F]UCB-H: First-in-Human Study
复制标题
新型突触囊泡蛋白2A（SV2A）放射性示踪剂[18F]UCB - H的生物分布与辐射剂量测定：首次人体研究
DOI：
10.1007/s11307-014-0820-6
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发表时间：
2015-08-01
影响因子：
3.1
通讯作者：
Salmon, E.
中科院分区：
文献类型：
--
作者：
Bretin, F.;Bahri, M. A.;Salmon, E.
[F-18]UCB-H是一种新型放射性示踪剂，对突触囊泡中表达的蛋白突触囊泡糖蛋白2A （SV2A）具有高亲和力。SV2A是左乙拉西坦的结合位点，左乙拉西坦是一种“一流的”抗癫痫药物，具有独特的作用机制，但对其作用机制仍知之甚少。本研究的目的是确定[F-18]UCB-H在人体临床试验中的生物分布和辐射剂量学，并根据生物医学研究指南建立注射限量。此外，临床辐射剂量测定结果与先前发表的临床前数据的估计进行了比较。在注射144.5 +/- 7.1 MBq（范围139.1-156.5 MBq） [F-18]UCB-H后，对5名健康男性志愿者进行了大约110分钟的动态全身正电子发射断层扫描/ x射线计算机断层扫描（PET/CT）成像。主要器官在CT图像上勾画，时间-活动曲线由共配准的动态PET发射扫描获得。膀胱只能在PET图像上勾画。时间积分活度系数采用梯形数值积分法计算曲线下面积。利用OLINDA/EXM的动态膀胱模块模拟基于PET活动的尿排泄数据，包括排尿。使用OLINDA/EXM计算辐射剂量。OLINDA/EXM 70公斤标准男性的有效剂量为1.54 × 10(-2) +/- 6.84 × 10（-4）毫西弗(mSv)/MBq，其中膀胱壁、胆囊壁和肝脏吸收剂量最高。脑是示踪剂的主要作用器官，接受的吸收剂量为1.89 x 10(-2) +/- 2.32 x 10(-3) mGy/MBq。首次对[F-18]UCB-H进行人体剂量学研究表明，该示踪剂与广泛使用的常见临床示踪剂具有相似的辐射负荷。美国的做法是单次注射的最高剂量为672 MBq，欧洲的做法是649 MBq，使辐射暴露低于建议限值。最近发表的从小鼠中推断的临床前剂量学数据提供了令人满意的全身剂量和有效剂量预测，但与人体数据相比，器官吸收剂量显示出显着差异。
[F-18]UCB-H is a novel radiotracer with a high affinity for synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a "first-in-class" antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [F-18]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data.Dynamic whole body positron emission tomography/X-ray computed tomography (PET/CT) imaging was performed over approximately 110 min on five healthy male volunteers after injection of 144.5 +/- 7.1 MBq (range, 139.1-156.5 MBq) of [F-18]UCB-H. Major organs were delineated on CT images, and time-activity curves were obtained from co-registered dynamic PET emission scans. The bladder could only be delineated on PET images. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET activities including voiding was also simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM.The effective dose to the OLINDA/EXM 70-kg standard male was 1.54 x 10(-2) +/- 6.84 x 10(-4) millisieverts (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving the highest absorbed dose. The brain, the tracer's main organ of interest, received an absorbed dose of 1.89 x 10(-2) +/- 2.32 x 10(-3) mGy/MBq.This first human dosimetry study of [F-18]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for US practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose but showed significant differences in organ absorbed doses compared to human data.