Barret Olivier, Hannestad Jonas, Vala Christine, Alagille David, Tavares Adriana, Laruelle Marc, Jennings Danna, Marek Ken, Russell David, Seibyl John, Tamagnan Gilles
Molecular NeuroImaging, LLC, New Haven, Connecticut; and
UCB Pharma SPRL, Braine-l'Alleud, Belgium.
J Nucl Med. 2015 Apr;56(4):586-91. doi: 10.2967/jnumed.114.152546. Epub 2015 Feb 19.
PET with selective adenosine 2A receptor (A2A) radiotracers can be used to study a variety of neurodegenerative and neuropsychiatric disorders in vivo and to support drug-discovery studies targeting A2A. The aim of this study was to describe the first in vivo evaluation of (18)F-MNI-444, a novel PET radiotracer for imaging A2A, in healthy human subjects.
Ten healthy human volunteers were enrolled in this study; 6 completed the brain PET studies and 4 participated in the whole-body PET studies. Arterial blood was collected for invasive kinetic modeling of the brain PET data. Noninvasive methods of data quantification were also explored. Test-retest reproducibility was evaluated in 5 subjects. Radiotracer distribution and dosimetry was determined using serial whole-body PET images acquired over 6 h post-radiotracer injection. Urine samples were collected to calculate urinary excretion.
After intravenous bolus injection, (18)F-MNI-444 rapidly entered the brain and displayed a distribution consistent with known A2A densities in the brain. Binding potentials ranging from 2.6 to 4.9 were measured in A2A-rich regions, with an average test-retest variability of less than 10%. The estimated whole-body radiation effective dose was approximately 0.023 mSv/MBq.
(18)F-MNI-444 is a useful PET radiotracer for imaging A2A in the human brain. The superior in vivo brain kinetic properties of (18)F-MNI-444, compared with previously developed A2A radiotracers, provide the opportunity to foster global use of in vivo A2A PET imaging in neuroscience research.
使用选择性腺苷2A受体（A2A）放射性示踪剂的正电子发射断层扫描（PET）可用于在体内研究多种神经退行性疾病和神经精神疾病，并支持针对A2A的药物研发研究。本研究的目的是描述新型PET放射性示踪剂（18）F-MNI-444在健康人体受试者中对A2A进行成像的首次体内评估。
10名健康人类志愿者参与本研究；6人完成了脑部PET研究，4人参与了全身PET研究。采集动脉血用于脑部PET数据的侵入性动力学建模。还探索了数据定量的非侵入性方法。在5名受试者中评估了重测重复性。使用放射性示踪剂注射后6小时内采集的系列全身PET图像确定放射性示踪剂分布和剂量学。收集尿液样本以计算尿排泄量。
静脉推注后，（18）F-MNI-444迅速进入大脑，并显示出与大脑中已知A2A密度一致的分布。在富含A2A的区域测得的结合潜能范围为2.6至4.9，重测平均变异性小于10%。估计的全身辐射有效剂量约为0.023 mSv/MBq。
（18）F-MNI-444是一种用于在人脑中对A2A进行成像的有用PET放射性示踪剂。与先前开发的A2A放射性示踪剂相比，（18）F-MNI-444具有优异的体内脑动力学特性，为促进在神经科学研究中全球使用体内A2A PET成像提供了机会。
