用于uPAR成像的PET示踪剂64Cu-DOTA-AE105的剂量测定。
Dosimetry of 64Cu-DOTA-AE105, a PET tracer for uPAR imaging.
作者信息
Persson Morten, El Ali Henrik H, Binderup Tina, Pfeifer Andreas, Madsen Jacob, Rasmussen Palle, Kjaer Andreas
机构信息
The Danish-Chinese Center for Proteases and Cancer; Department of Clinical Physiology, Nuclear Medicine & PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Physiology, Nuclear Medicine & PET, Center for Diagnostic Investigations, Rigshospitalet, Copenhagen, Denmark; Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
出版信息
Nucl Med Biol. 2014 Mar;41(3):290-5. doi: 10.1016/j.nucmedbio.2013.12.007. Epub 2013 Dec 18.
UNLABELLED
(64)Cu-DOTA-AE105 is a novel positron emission tomography (PET) tracer specific to the human urokinase-type plasminogen activator receptor (uPAR). In preparation of using this tracer in humans, as a new promising method to distinguish between indolent and aggressive cancers, we have performed PET studies in mice to evaluate the in vivo biodistribution and estimate human dosimetry of (64)Cu-DOTA-AE105.
METHODS
Five mice received iv tail injection of (64)Cu-DOTA-AE105 and were PET/CT scanned 1, 4.5 and 22 h post injection. Volume-of-interest (VOI) were manually drawn on the following organs: heart, lung, liver, kidney, spleen, intestine, muscle, bone and bladder. The activity concentrations in the mentioned organs [%ID/g] were used for the dosimetry calculation. The %ID/g of each organ at 1, 4.5 and 22 h was scaled to human value based on a difference between organ and body weights. The scaled values were then exported to OLINDA software for computation of the human absorbed doses. The residence times as well as effective dose equivalent for male and female could be obtained for each organ. To validate this approach, of human projection using mouse data, five mice received iv tail injection of another (64)Cu-DOTA peptide-based tracer, (64)Cu-DOTA-TATE, and underwent same procedure as just described. The human dosimetry estimates were then compared with observed human dosimetry estimate recently found in a first-in-man study using (64)Cu-DOTA-TATE.
RESULTS
Human estimates of (64)Cu-DOTA-AE105 revealed the heart wall to receive the highest dose (0.0918 mSv/MBq) followed by the liver (0.0815 mSv/MBq), All other organs/tissue were estimated to receive doses in the range of 0.02-0.04 mSv/MBq. The mean effective whole-body dose of (64)Cu-DOTA-AE105 was estimated to be 0.0317 mSv/MBq. Relatively good correlation between human predicted and observed dosimetry estimates for (64)Cu-DOTA-TATE was found. Importantly, the effective whole body dose was predicted with very high precision (predicted value: 0.0252 mSv/Mbq, Observed value: 0.0315 mSv/MBq) thus validating our approach for human dosimetry estimation.
CONCLUSION
Favorable dosimetry estimates together with previously reported uPAR PET data fully support human testing of (64)Cu-DOTA-AE105.
未标记
（64）Cu-DOTA-AE105是一种新型的正电子发射断层扫描（PET）示踪剂，对人尿激酶型纤溶酶原激活剂受体（uPAR）具有特异性。在准备将这种示踪剂用于人体时，作为一种区分惰性癌症和侵袭性癌症的新的有前景的方法，我们在小鼠身上进行了PET研究，以评估（64）Cu-DOTA-AE105的体内生物分布并估计人体剂量。
方法
五只小鼠经尾静脉注射（64）Cu-DOTA-AE105，并在注射后1、4.5和22小时进行PET/CT扫描。在以下器官上手动绘制感兴趣区（VOI）：心脏、肺、肝脏、肾脏、脾脏、肠道、肌肉、骨骼和膀胱。将上述器官中的活度浓度[％ID/g]用于剂量计算。根据器官和体重之间的差异，将1、4.5和22小时时每个器官的％ID/g按比例换算为人体值。然后将换算后的值导出到OLINDA软件中，以计算人体吸收剂量。可以获得每个器官的驻留时间以及男性和女性的有效剂量当量。为了验证这种使用小鼠数据进行人体投影的方法，五只小鼠经尾静脉注射了另一种基于（64）Cu-DOTA肽的示踪剂（64）Cu-DOTA-TATE，并进行了与上述相同的操作。然后将人体剂量估计值与最近在一项使用（64）Cu-DOTA-TATE的人体首次研究中观察到的人体剂量估计值进行比较。
结果
（64）Cu-DOTA-AE105的人体估计显示，心脏壁接受的剂量最高（0.0918 mSv/MBq），其次是肝脏（0.0815 mSv/MBq），所有其他器官/组织估计接受的剂量在0.02 - 0.04 mSv/MBq范围内。（64）Cu-DOTA-AE105的平均有效全身剂量估计为0.0317 mSv/MBq。发现（64）Cu-DOTA-TATE的人体预测剂量估计值与观察到的剂量估计值之间具有较好的相关性。重要的是，有效全身剂量的预测精度非常高（预测值：0.0252 mSv/Mbq，观察值：0.0315 mSv/MBq），从而验证了我们用于人体剂量估计的方法。
结论
良好的剂量估计以及先前报道的uPAR PET数据充分支持对（64）Cu-DOTA-AE105进行人体测试。
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