Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans.
Biodistribution and radiation dosimetry of the integrin marker 18F-RGD-K5 determined from whole-body PET/CT in monkeys and humans.
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DOI：
10.2967/jnumed.111.088955
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Yu JQ
中科院分区：
文献类型：
--
作者：
Doss M;Kolb HC;Zhang JJ;Bélanger MJ;Stubbs JB;Stabin MG;Hostetler ED;Alpaugh RK;von Mehren M;Walsh JC;Haka M;Mocharla VP;Yu JQ
18F-RGD-K5已被开发为正电子发射断层扫描（PET）的αvβ3整合素标记物。本研究的目的是通过对猴子和人类进行全身PET/CT扫描，确定18F-RGD-K5的生物分布并估计其辐射剂量。在3只恒河猴（167±19 MBq）和4名健康人（583±78 MBq）静脉注射18F-RGD-K5后，连续进行全身PET/CT扫描。在人类中，在PET/CT扫描之间收集血液样本，并评估18F-RGD-K5的稳定性。在两次扫描之间还收集了尿液，以确定尿液中排泄的总活性。对PET扫描结果进行分析，以确定不同器官对放射性示踪剂的摄取。使用OLINDA/EXM软件计算基于人和猴生物分布的人体辐射剂量。18F-RGD-K5在注射后90分钟内在人血中代谢稳定，并以12分钟的中场休息时间迅速从血池中清除。对于猴子和人类，在肾脏、膀胱、肝脏和胆囊中观察到18F-RGD-K5的摄取增加，人类注射后1小时的平均标准化摄取值分别约为20、50、4和10。利用人体生物分布数据，计算有效剂量为31±1 μSv/MBq， 4.8 h膀胱排尿模型膀胱壁吸收剂量最高，为376±19 μGy/MBq。对于1 h排尿模型，剂量分别降至15±1 μSv/MBq和103±4 μGy/MBq。典型注射活度为555mbq时，4.8小时模型有效剂量为17.2±0.6 mSv， 1小时模型有效剂量为8.3±0.4 mSv。根据猴子生物分布数据，这两种模型对人体的有效剂量分别为22.2±2.4 mSv和12.8±0.2 mSv。18F-RGD-K5在猴子和人类中的生物分布相似，在膀胱、肝脏和肾脏中的摄取增加。18F-RGD-K5通过肾脏系统迅速清除。膀胱壁受到的辐射剂量最高，被认为是关键器官。全身有效剂量和膀胱剂量都可以通过频繁排尿而降低。18F-RGD-K5可以安全地用于人类αvβ3整合素表达的成像。
18F-RGD-K5 has been developed as an αvβ3 integrin marker for positron emission tomography (PET). The purpose of this study was to determine the biodistribution and estimate the radiation dose from 18F-RGD-K5 using whole body PET/CT scans in monkeys and humans. Successive whole body PET/CT scans were performed after intravenous injection of 18F-RGD-K5 in three rhesus monkeys (167±19 MBq) and four healthy humans (583±78 MBq). In humans, blood samples were collected between the PET/CT scans, and stability of 18F-RGD-K5 was assessed. Urine was also collected between the scans, to determine the total activity excreted in urine. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on human and monkey biodistributions. 18F-RGD-K5 was metabolically stable in human blood up to 90 minutes after injection, and it cleared rapidly from the blood pool with a 12 minute half-time. For both monkeys and humans, increased 18F-RGD-K5 uptake was observed in kidneys, bladder, liver, and gallbladder, with mean standardized uptake values at 1 hr after injection for humans being approximately 20, 50, 4, and 10 respectively. Using human biodistribution data, calculated effective dose was 31±1 μSv/MBq, and urinary bladder wall had the highest absorbed dose at 376±19 μGy/MBq using 4.8 hr bladder voiding model. For 1 hr voiding model, these doses reduced to 15±1 μSv/MBq and 103±4 μGy/MBq respectively. For a typical injected activity of 555 MBq, the effective dose would be 17.2±0.6 mSv for 4.8 hr model, reducing to 8.3±0.4 mSv for 1 hr model. Using monkey biodistribution data, the effective dose to humans for these two models would be 22.2±2.4 mSv and 12.8±0.2 mSv respectively. The biodistribution profile of 18F-RGD-K5 in monkeys and humans was similar with increased uptake in bladder, liver and kidneys. There was rapid clearance of 18F-RGD-K5 through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both whole body effective dose and bladder dose can be reduced by voiding more frequently. 18F-RGD-K5 can be used safely for imaging αvβ3 integrin expression in humans.
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影响因子：
64.5
作者：
BROOKS, PC;MONTGOMERY, AMP;CHERESH, DA
通讯作者：
CHERESH, DA
影响因子：
7.5
作者：
Vonlaufen, A;Wiedle, G;Imhof, BA
通讯作者：
Imhof, BA
影响因子：
1.2
作者：
Walsh, Joseph C.;Kolb, Hartmuth C.
通讯作者：
Kolb, Hartmuth C.
影响因子：
9.8
作者：
Barrett, PHR;Bell, BM;Foster, DM
通讯作者：
Foster, DM
影响因子：
9.2
作者：
Brown, Aaron P.;Citrin, Deborah E.;Camphausen, Kevin A.
通讯作者：
Camphausen, Kevin A.