一项关于F-GP1正电子发射断层扫描用于急性动脉血栓成像的1期人体首次研究。
A phase 1, first-in-human study of F-GP1 positron emission tomography for imaging acute arterial thrombosis.
作者信息
Chae Sun Young, Kwon Tae-Won, Jin Soyoung, Kwon Sun U, Sung Changhwan, Oh Seung Jun, Lee Sang Ju, Oh Jungsu S, Han Youngjin, Cho Yong-Pil, Lee Narae, Kim Ji Young, Koglin Norman, Berndt Mathias, Stephens Andrew W, Moon Dae Hyuk
机构信息
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
Department of Vascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
出版信息
EJNMMI Res. 2019 Jan 7;9(1):3. doi: 10.1186/s13550-018-0471-8.
BACKGROUND
F-GP1 is a novel positron emission tomography (PET) tracer that targets glycoprotein IIb/IIIa receptors on activated platelets. The study objective was to explore the feasibility of directly imaging acute arterial thrombosis (AAT) with F-GP1 PET/computed tomography (PET/CT) and to quantitatively assess F-GP1 uptake. Safety, biodistribution, pharmacokinetics and metabolism were also evaluated.
METHODS
Adult patients who had signs or symptoms of AAT or had recently undergone arterial intervention or surgery within 14 days prior to F-GP1 PET/CT were eligible for inclusion. The AAT focus was demonstrated by conventional imaging within the 5 days prior to F-GP1 administration. Whole-body dynamic F-GP1 PET/CT images were acquired for up to 140 min after injection of 250 MBq of F-GP1. Venous plasma samples were analysed to determine F-GP1 clearance and metabolite formation.
RESULTS
Among the ten eligible patients assessed, underlying diseases were abdominal aortic aneurysm with endovascular repair (n = 6), bypass surgery and stent placement (n = 1), endarterectomy (n = 1), arterial dissection (n = 1) and acute cerebral infarction (n = 1). F-GP1 administration and PET/CT procedures were well tolerated, with no drug-related adverse events. All patients showed high initial F-GP1 uptake in the spleen, kidney and blood pool, followed by rapid clearance. Unmetabolised plasma F-GP1 levels peaked at 4 min post-injection and decreased over time until 120 min. The overall image quality was sufficient for diagnosis in all patients and AAT foci were detected in all participants. The F-GP1 uptake in AAT foci remained constant from 7 min after injection and began to separate from the blood pool after 20 min. The median standardised uptake value of AAT was 5.0 (range 2.4-7.9) at 120 min post-injection. The median ratio of standardised uptake value of AAT foci to the mean blood pool activity was 3.4 (range 2.0-6.3) at 120 min.
CONCLUSIONS
F-GP1 is a safe and promising novel PET tracer for imaging AAT with a favourable biodistribution and pharmacokinetic profile.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02864810 , Registered August 3, 2016.
背景
F-GP1是一种新型正电子发射断层扫描（PET）示踪剂，可靶向活化血小板上的糖蛋白IIb/IIIa受体。本研究的目的是探讨使用F-GP1 PET/计算机断层扫描（PET/CT）直接成像急性动脉血栓形成（AAT）的可行性，并定量评估F-GP1的摄取情况。同时还评估了安全性、生物分布、药代动力学和代谢情况。
方法
有AAT体征或症状，或在F-GP1 PET/CT检查前14天内近期接受过动脉介入治疗或手术的成年患者符合纳入标准。在给予F-GP1前5天内通过传统成像显示AAT病灶。注射250 MBq的F-GP1后，采集全身动态F-GP1 PET/CT图像，最长持续140分钟。分析静脉血浆样本以确定F-GP1的清除率和代谢产物形成情况。
结果
在评估的10名符合条件的患者中，基础疾病包括腹主动脉瘤伴血管腔内修复术（n = 6）、搭桥手术和支架置入术（n = 1）、动脉内膜切除术（n = 1）、动脉夹层（n = 1）和急性脑梗死（n = 1）。F-GP1给药和PET/CT检查耐受性良好，未出现与药物相关的不良事件。所有患者脾脏、肾脏和血池均显示出较高的初始F-GP1摄取，随后迅速清除。未代谢的血浆F-GP1水平在注射后4分钟达到峰值，随时间下降直至120分钟。所有患者的整体图像质量足以用于诊断，所有参与者均检测到AAT病灶。AAT病灶中的F-GP1摄取在注射后7分钟保持恒定，20分钟后开始与血池分离。注射后120分钟，AAT的标准化摄取值中位数为5.0（范围2.4 - 7.9）。120分钟时，AAT病灶标准化摄取值与平均血池活性的中位数比值为3.4（范围2.0 - 6.3）。
结论
F-GP1是一种安全且有前景的新型PET示踪剂，用于AAT成像具有良好的生物分布和药代动力学特征。
试验注册
ClinicalTrials.gov标识符：NCT02864810，2016年8月3日注册。
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