Blood Clearance Kinetics, Biodistribution, and Radiation Dosimetry of a Kit-Formulated Integrin αvβ3-Selective Radiotracer 99mTc-3PRGD2 in Non-Human Primates
Blood Clearance Kinetics, Biodistribution, and Radiation Dosimetry of a Kit-Formulated Integrin αvβ3-Selective Radiotracer 99mTc-3PRGD2 in Non-Human Primates
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DOI：
10.1007/s11307-010-0385-y
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发表时间：
2011-08-01
影响因子：
3.1
通讯作者：
Wang, Fan
中科院分区：
文献类型：
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作者：
Jia, Bing;Liu, Zhaofei;Wang, Fan
Tc-99m-3PRGD(2)是一种tc -99m标记的二聚环RGD肽，具有增强的受体结合亲和力，并且在裸鼠模型中改善了整合素α (v) β(3)表达的体内成像动力学。为了加速其临床转化，我们在此报道了对试剂盒配制的Tc-99m-3PRGD(2)在健康食蟹灵长类动物中的血液清除动力学、生物分布和辐射剂量学的评估。对健康食蟹灵长类动物（4.1 +/- 0.7 kg, n = 5）进行麻醉，注射类似于555 MBq的Tc-99m-3PRGD后，通过股静脉导管在不同时间点采集静脉血(2)。在给予类似于555 MBq的Tc-99m-3PRGD(2)后，用双头单光子发射计算机断层扫描系统对非人灵长类动物进行了连续全身扫描，并计算了辐射剂量学估计。Tc-99m-3PRGD(2)可以很容易地从冷冻干燥试剂盒中获得，具有高放射化学纯度（> 95%）和高比活性（类似于5 Ci/mu mol）。Tc-99m-3PRGD(2)具有快速的血液清除率，注射后60分钟血液循环中残留的初始放射性不到1%。重复给药后4周未见不良反应。全身图像显示Tc-99m-3PRGD在肾脏的高摄取(2)和膀胱内的高放射性积聚，表明该示踪剂在肾脏的快速清除。Tc-99m-3PRGD(2)辐射剂量最高的部位为肾脏（13.2 +/- 1.08 mu Gy/MBq）和膀胱壁（33.1 +/- 1.91 mu Gy/MBq）。Tc-99m-3PRGD(2)可以使用试剂盒配方随时获得。该示踪剂安全且耐受性良好，在非人类灵长类动物中未发生不良事件。Tc-99m-3PRGD(2)用于人类整合素α (v) β(3)的无创成像的进一步临床测试和翻译是有必要的。
Tc-99m-3PRGD(2) is a Tc-99m-labeled dimeric cyclic RGD peptide with increased receptor binding affinity and improved kinetics for in vivo imaging of integrin alpha(v)beta(3) expression in nude mouse model. To accelerate its clinical translation, we reported here the evaluation of the kit-formulated Tc-99m-3PRGD(2) in healthy cynomolgus primates for its blood clearance kinetics, biodistribution, and radiation dosimetry.Healthy cynomolgus primates (4.1 +/- 0.7 kg, n = 5) were anesthetized, and the venous blood samples were collected via a femoral vein catheter at various time points after injection of similar to 555 MBq of Tc-99m-3PRGD(2). Serial whole-body scans were performed with a dual-head single photon emission computed tomography system after administering similar to 555 MBq of Tc-99m-3PRGD(2) in the non-human primates, and the radiation dosimetry estimate was calculated.Tc-99m-3PRGD(2) could be easily obtained from freeze-dried kits with high radiochemical purity (> 95%) and high specific activity (similar to 5 Ci/mu mol). Tc-99m-3PRGD(2) had a rapid blood clearance with less than 1% of the initial radioactivity remaining in the blood circulation at 60 min postinjection. No adverse reactions were observed up to 4 weeks after the repeated dosing. The whole-body images exhibited high kidney uptake of Tc-99m-3PRGD(2) and high radioactivity accumulation in the bladder, demonstrating the rapid renal clearance of this tracer. The highest radiation doses of Tc-99m-3PRGD(2) were found in the kidneys (13.2 +/- 1.08 mu Gy/MBq) and the bladder wall (33.1 +/- 1.91 mu Gy/MBq).Tc-99m-3PRGD(2) can be readily available using the kit formulation. This tracer is safe and well tolerated, and no adverse events occurred in non-human primates. Further clinical testing and translation of Tc-99m-3PRGD(2) for noninvasive imaging of integrin alpha(v)beta(3) in humans are warranted.