Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
J Nucl Med. 2013 Aug;54(8):1302-7. doi: 10.2967/jnumed.113.119891. Epub 2013 Jun 26.
N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM) is a potential radioligand for mapping metabotropic glutamate receptor type 1 (mGluR1) in the brain by PET. The present study was performed to determine the safety, distribution, radiation dosimetry, and initial brain imaging of (11)C-ITMM in healthy human subjects.
The multiorgan biodistribution and radiation dosimetry of (11)C-ITMM were assessed in 3 healthy human subjects, who underwent 2-h whole-body PET scans. Radiation dosimetry was estimated from the normalized number of disintegrations of source organs using the OLINDA/EXM program. Five healthy human subjects underwent 90-min dynamic (11)C-ITMM scans of brain regions with arterial blood sampling. For anatomic coregistration, T1-weighted MR imaging was performed. Metabolites in plasma and urine samples were analyzed by high-performance liquid chromatography. (11)C-ITMM uptake was assessed quantitatively using a 2-tissue-compartment model.
There were no serious adverse events in any of the subjects throughout the study period. (11)C-ITMM PET demonstrated high uptake in the urinary bladder and gallbladder, indicating both urinary and fecal excretion of radioactivity. The absorbed dose (μGy/MBq) was highest in the urinary bladder wall (13.2 ± 3.5), small intestine (9.8 ± 1.7), and liver (9.1 ± 2.0). The estimated effective dose for (11)C-ITMM was 4.6 ± 0.3 μSv/MBq. (11)C-ITMM showed a gradual increase of radioactivity in the cerebellar cortex. The total distribution volume in the brain regions ranged from 2.61 ± 0.30 (cerebellar cortex) to 0.52 ± 0.17 (pons), and the rank order of the corresponding total distribution volume of (11)C-ITMM was cerebellar cortex > thalamus > frontal cortex > striatum ≈ pons, which was consistent with the known distribution of mGluR1 in the primate brain. The rate of (11)C-ITMM metabolism in plasma was moderate: at 60 min after injection, 62.2% ± 8.2% of the radioactivity in plasma was intact parent compound.
The initial findings of the present study indicated that (11)C-ITMM PET is feasible for imaging of mGluR1 in the brain. The low effective dose will permit serial examinations in the same subjects.
评估放射性配体 N-[4-[6-(异丙基氨基)嘧啶-4-基]-1,3-噻唑-2-基]-4-(11)C-甲氧基-N-甲基苯甲酰胺 ((11)C-ITMM) 在健康人体中的安全性、分布、辐射剂量和初步脑成像。
3 名健康志愿者接受了 2 小时全身 PET 扫描，评估了 (11)C-ITMM 的多器官生物分布和辐射剂量。使用 OLINDA/EXM 程序，从源器官的归一化放射性衰变数估计辐射剂量。5 名健康志愿者进行了 90 分钟的脑区动态 (11)C-ITMM 扫描，并进行动脉采血。为了进行解剖配准，进行了 T1 加权磁共振成像。通过高效液相色谱法分析血浆和尿液样本中的代谢物。使用 2 组织室模型定量评估 (11)C-ITMM 摄取。
在整个研究期间，所有受试者均无严重不良事件。(11)C-ITMM PET 显示在膀胱和胆囊中有高摄取，表明放射性核素通过尿液和粪便排泄。吸收剂量（μGy/MBq）最高的器官是膀胱壁（13.2 ± 3.5）、小肠（9.8 ± 1.7）和肝脏（9.1 ± 2.0）。(11)C-ITMM 的估算有效剂量为 4.6 ± 0.3 μSv/MBq。(11)C-ITMM 在小脑皮质中显示放射性逐渐增加。脑区的总分布容积范围为 2.61 ± 0.30（小脑皮质）至 0.52 ± 0.17（脑桥），相应的 (11)C-ITMM 总分布容积的顺序为小脑皮质＞丘脑＞额叶皮质＞纹状体≈脑桥，与灵长类动物大脑中 mGluR1 的已知分布一致。血浆中 (11)C-ITMM 代谢率适中：注射后 60 分钟，血浆中 62.2%±8.2%的放射性为完整的母体化合物。
本研究的初步结果表明，(11)C-ITMM PET 可行用于脑内 mGluR1 的成像。低有效剂量将允许在同一受试者中进行连续检查。
