Medical Isotopes Research Center, Peking University, Beijing, China.
Mol Imaging Biol. 2011 Aug;13(4):730-6. doi: 10.1007/s11307-010-0385-y.
(99m)Tc-3PRGD(2) is a (99m)Tc-labeled dimeric cyclic RGD peptide with increased receptor binding affinity and improved kinetics for in vivo imaging of integrin α(v)β(3) expression in nude mouse model. To accelerate its clinical translation, we reported here the evaluation of the kit-formulated (99m)Tc-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 ~555 MBq of (99m)Tc-3PRGD(2). Serial whole-body scans were performed with a dual-head single photon emission computed tomography system after administering ~555 MBq of (99m)Tc-3PRGD(2) in the non-human primates, and the radiation dosimetry estimate was calculated.
(99m)Tc-3PRGD(2) could be easily obtained from freeze-dried kits with high radiochemical purity (>95%) and high specific activity (~5 Ci/μmol). (99m)Tc-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 (99m)Tc-3PRGD(2) and high radioactivity accumulation in the bladder, demonstrating the rapid renal clearance of this tracer. The highest radiation doses of (99m)Tc-3PRGD(2) were found in the kidneys (13.2 ± 1.08 μGy/MBq) and the bladder wall (33.1 ± 1.91 μGy/MBq).
(99m)Tc-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 (99m)Tc-3PRGD(2) for noninvasive imaging of integrin α(v)β(3) in humans are warranted.
(99m)Tc-3PRGD(2) 是一种 (99m)Tc 标记的二聚环 RGD 肽，具有更高的受体结合亲和力和改善的动力学特性，可用于在裸鼠模型中体内成像整合素 α(v)β(3)的表达。为了加速其临床转化，我们在此报告了试剂盒形式的 (99m)Tc-3PRGD(2) 在健康食蟹猴中的血液清除动力学、生物分布和辐射剂量学评估。
健康食蟹猴（4.1±0.7 kg，n=5）麻醉后，通过股静脉导管在注射约 555 MBq 的 (99m)Tc-3PRGD(2) 后不同时间点采集静脉血样。在非人类灵长类动物中注射约 555 MBq 的 (99m)Tc-3PRGD(2) 后，使用双探头单光子发射计算机断层扫描系统进行连续全身扫描，并计算辐射剂量估算值。
(99m)Tc-3PRGD(2) 可从冻干试剂盒中轻松获得，具有高放射化学纯度（>95%）和高比活度（~5 Ci/μmol）。(99m)Tc-3PRGD(2) 具有快速的血液清除特性，在注射后 60 分钟时，血液循环中不到 1%的初始放射性残留。重复给药后 4 周内未观察到不良反应。全身图像显示 (99m)Tc-3PRGD(2) 在肾脏中的摄取量高，膀胱中的放射性积累高，表明该示踪剂具有快速的肾脏清除能力。(99m)Tc-3PRGD(2) 的最高辐射剂量分别位于肾脏（13.2±1.08 μGy/MBq）和膀胱壁（33.1±1.91 μGy/MBq）。
(99m)Tc-3PRGD(2) 可通过试剂盒形式获得。该示踪剂安全且耐受良好，在非人类灵长类动物中未发生不良事件。需要进一步进行临床测试，并将 (99m)Tc-3PRGD(2) 用于非侵入性成像整合素 α(v)β(3) 在人类中的转化。
