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使用啮齿动物和非人类灵长类动物估计D特异性正电子发射断层显像放射性配体[F]氟哌利多的吸收辐射剂量测定法。

Absorbed radiation dosimetry of the D-specific PET radioligand [F]FluorTriopride estimated using rodent and nonhuman primate.

作者信息

Laforest Richard, Karimi Morvarid, Moerlein Stephen M, Xu Jinbin, Flores Hubert P, Bognar Christopher, Li Aixiao, Mach Robert H, Perlmutter Joel S, Tu Zhude

机构信息

Mallinckrodt Institute of Radiology, School of Medicine, Washington University St. Louis, MO 63110, USA.

Department of Neurology, School of Medicine, Washington University St. Louis, MO 63110, USA.

出版信息

Am J Nucl Med Mol Imaging. 2016 Nov 30;6(6):301-309. eCollection 2016.

Abstract

[F]FluorTriopride ([F]FTP) is a dopamine D-receptor preferring radioligand with potential for investigation of neuropsychiatric disorders including Parkinson disease, dystonia and schizophrenia. Here we estimate human radiation dosimetry for [F]FTP based on the biodistribution in rodents and distribution in nonhuman primates. Biodistribution data were generated using male and female Sprague-Dawley rats injected with ~370 KBq of [F]FTP and euthanized at 5, 30, 60, 120, and 240 min. Organs of interest were dissected, weighed and assayed for radioactivity content. PET imaging studies were performed in two male and one female administered 143-190 MBq of [F]FTP and scanned whole-body in sequential sections. Organ residence times were calculated based on organ time activity curves (TAC) created from regions of Interest. OLINDA/EXM 1.1 was used to estimate human radiation dosimetry based on scaled organ residence times. In the rodent, the highest absorbed radiation dose was the upper large intestines (0.32-0.49 mGy/MBq), with an effective dose of 0.07 mSv/MBq in males and 0.1 mSv/MBq in females. For the nonhuman primate, however, the gallbladder wall was the critical organ (1.81 mGy/MBq), and the effective dose was 0.02 mSv/MBq. The species discrepancy in dosimetry estimates for [F]FTP based on rat and primate data can be attributed to the slower transit of tracer through the hepatobiliary track of the primate compared to the rat, which lacks a gallbladder. Out findings demonstrate that the nonhuman primate model is more appropriate model for estimating human absorbed radiation dosimetry when hepatobiliary excretion plays a major role in radiotracer elimination.

摘要

氟哌三氟丙嗪([F]FTP)是一种对多巴胺D受体具有选择性的放射性配体,具有用于研究包括帕金森病、肌张力障碍和精神分裂症在内的神经精神疾病的潜力。在此,我们基于啮齿动物的生物分布和非人灵长类动物的分布情况来估算[F]FTP对人体的辐射剂量。生物分布数据是通过向雄性和雌性斯普拉格-道利大鼠注射约370千贝克勒尔的[F]FTP,并在5、30、60、120和240分钟时实施安乐死来生成的。解剖感兴趣的器官,称重并测定其放射性含量。对两只雄性和一只雌性非人灵长类动物注射143 - 190兆贝克勒尔的[F]FTP,并对其进行全身连续断层扫描的PET成像研究。基于从感兴趣区域创建的器官时间-活度曲线(TAC)来计算器官驻留时间。使用OLINDA/EXM 1.1基于按比例缩放的器官驻留时间来估算人体辐射剂量。在啮齿动物中,吸收辐射剂量最高的是上大肠(0.32 - 0.49毫戈瑞/兆贝克勒尔),雄性的有效剂量为0.07毫希沃特/兆贝克勒尔,雌性为0.1毫希沃特/兆贝克勒尔。然而,对于非人灵长类动物,胆囊壁是关键器官(1.81毫戈瑞/兆贝克勒尔),有效剂量为0.02毫希沃特/兆贝克勒尔。基于大鼠和灵长类动物数据对[F]FTP剂量测定估计值的物种差异可归因于示踪剂在灵长类动物肝胆系统中的转运比大鼠慢,大鼠没有胆囊。我们的研究结果表明,当肝胆排泄在放射性示踪剂消除中起主要作用时,非人灵长类动物模型是估算人体吸收辐射剂量更合适的模型。

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本文引用的文献

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Radiation dosimetry of [(18)F]VAT in nonhuman primates.非人灵长类动物中[(18)F]VAT的辐射剂量测定
EJNMMI Res. 2015 Dec;5(1):73. doi: 10.1186/s13550-015-0149-4. Epub 2015 Dec 10.

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