Beinat Corinne, Patel Chirag B, Haywood Tom, Shen Bin, Naya Lewis, Gandhi Harsh, Holley Dawn, Khalighi Mehdi, Iagaru Andrei, Davidzon Guido, Gambhir Sanjiv Sam
Molecular Imaging Program at Stanford, Department of Radiology, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Division of Neuro-Oncology, Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA, 94305, USA.
Eur J Nucl Med Mol Imaging. 2020 Aug;47(9):2123-2130. doi: 10.1007/s00259-020-04687-0. Epub 2020 Jan 15.
To assess the safety, biodistribution, and radiation dosimetry of the novel positron emission tomography (PET) radiopharmaceutical 1-((2-fluoro-6-[[F]]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([F]DASA-23) in healthy volunteers.
We recruited 5 healthy volunteers who provided a written informed consent. Volunteers were injected with 295.0 ± 8.2 MBq of [F]DASA-23 intravenously. Immediately following injection, a dynamic scan of the brain was acquired for 15 min. This was followed by serial whole-body PET/MRI scans acquired up to 3 h post-injection. Blood samples were collected at regular intervals, and vital signs monitored pre- and post-radiotracer administration. Regions of interest were drawn around multiple organs, time-activity curves were calculated, and organ uptake and dosimetry were estimated with OLINDA/EXM (version 1.1) software.
All subjects tolerated the PET/MRI examination, without adverse reactions to [F]DASA-23. [F]DASA-23 passively crossed the blood-brain barrier, followed by rapid clearance from the brain. High accumulation of [F]DASA-23 was noted in organs such as the gallbladder, liver, small intestine, and urinary bladder, suggesting hepatobiliary and urinary clearance. The effective dose of [F]DASA-23 was 23.5 ± 5.8 μSv/MBq.
We successfully completed a pilot first-in-human study of [F]DASA-23. Our results indicate that [F]DASA-23 can be used safely in humans to evaluate pyruvate kinase M2 levels. Ongoing studies are evaluating the ability of [F]DASA-23 to visualize intracranial malignancies, NCT03539731.
ClinicalTrials.gov , NCT03539731 (registered 28 May 2018).
评估新型正电子发射断层扫描（PET）放射性药物1-((2-氟-6-[[F]]氟苯基)磺酰基)-4-((4-甲氧基苯基)磺酰基)哌嗪（[F]DASA-23）在健康志愿者中的安全性、生物分布和辐射剂量学。
招募5名提供书面知情同意书的健康志愿者。志愿者静脉注射295.0±8.2 MBq的[F]DASA-23。注射后立即进行15分钟的脑部动态扫描。随后在注射后3小时内进行系列全身PET/MRI扫描。定期采集血样，并在注射放射性示踪剂前后监测生命体征。在多个器官周围绘制感兴趣区域，计算时间-活性曲线，并用OLINDA/EXM（1.1版）软件估计器官摄取和剂量学。
所有受试者均耐受PET/MRI检查，对[F]DASA-23无不良反应。[F]DASA-23被动穿过血脑屏障，随后迅速从脑中清除。在胆囊、肝脏、小肠和膀胱等器官中观察到[F]DASA-23的高蓄积，提示肝胆和尿液清除。[F]DASA-23的有效剂量为23.5±5.8 μSv/MBq。
我们成功完成了[F]DASA-23的首次人体试验性研究。我们的结果表明，[F]DASA-23可安全用于人体评估丙酮酸激酶M2水平。正在进行的研究正在评估[F]DASA-23可视化颅内恶性肿瘤的能力，NCT03539731。
ClinicalTrials.gov，NCT03539731（2018年5月28日注册）。
