Tavares Adriana Alexandre S, Caillé Fabien, Barret Olivier, Papin Caroline, Lee Hsiaoju, Morley Thomas J, Fowles Krista, Holden Daniel, Seibyl John P, Alagille David, Tamagnan Gilles D
Molecular NeuroImaging, LLC, New Haven, CT, USA.
Molecular NeuroImaging, LLC, New Haven, CT, USA; Institute for Neurodegenerative Disorders, New Haven, CT, USA.
Nucl Med Biol. 2014 May-Jun;41(5):432-9. doi: 10.1016/j.nucmedbio.2014.02.005. Epub 2014 Feb 28.
A new radiotracer for imaging the serotonin 4 receptors (5-HT4) in brain, [¹⁸F]MNI-698, was recently developed by our group. Evaluation in nonhuman primates indicates the novel radiotracer holds promise as an imaging agent of 5-HT4 in brain. This paper aims to describe the whole-body biodistribution and dosimetry estimates of [¹⁸F]MNI-698.
Whole-body positron emission tomography (PET) images were acquired over 240 minutes after intravenous bolus injection of [¹⁸F]MNI-698 in adult rhesus monkeys. Different models were investigated for quantification of radiation absorbed and effective doses using OLINDA/EXM 1.0 software.
The radiotracer main elimination route was found to be urinary and the critical organ was the urinary bladder. Modeling of the urinary bladder voiding interval had a considerable effect on the estimated effective dose. Normalization of rhesus monkeys' organs and whole-body masses to human equivalent reduced the calculated dosimetry values. The effective dose ranged between 0.017 and 0.027 mSv/MBq.
The dosimetry estimates, obtained when normalizing organ and whole-body weights and applying the urinary bladder model, indicate that the radiation doses from [¹⁸F]MNI-698 comply with limits and guidelines recommended by key regulatory authorities that govern the translation of radiotracers to human clinical trials. The timing of urinary bladder emptying should be considered when designing future clinical protocols with [¹⁸F]MNI-698, in order to minimize the subject absorbed doses.
我们团队最近研发出一种用于脑内5-羟色胺4受体(5-HT4)成像的新型放射性示踪剂[¹⁸F]MNI-698。对非人灵长类动物的评估表明,这种新型放射性示踪剂有望成为脑内5-HT4的成像剂。本文旨在描述[¹⁸F]MNI-698的全身生物分布及剂量学估算。
在成年恒河猴静脉推注[¹⁸F]MNI-698后240分钟内采集全身正电子发射断层扫描(PET)图像。使用OLINDA/EXM 1.0软件研究不同模型以量化辐射吸收剂量和有效剂量。
发现该放射性示踪剂的主要消除途径是经尿液排出,关键器官是膀胱。膀胱排尿间隔的建模对估算有效剂量有显著影响。将恒河猴的器官和全身质量归一化为人类等效质量可降低计算出的剂量学值。有效剂量范围在0.017至0.027 mSv/MBq之间。
在对器官和全身重量进行归一化并应用膀胱模型时获得的剂量学估算表明,[¹⁸F]MNI-698的辐射剂量符合关键监管机构推荐的将放射性示踪剂转化为人体临床试验的限值和指南。在设计未来使用[¹⁸F]MNI-698的临床方案时,应考虑膀胱排空时间,以尽量减少受试者的吸收剂量。