Radiation Dosimetry of the Fibrin-Binding Probe ⁶⁴Cu-FBP8 and Its Feasibility for PET Imaging of Deep Vein Thrombosis and Pulmonary Embolism in Rats.
Radiation Dosimetry of the Fibrin-Binding Probe ⁶⁴Cu-FBP8 and Its Feasibility for PET Imaging of Deep Vein Thrombosis and Pulmonary Embolism in Rats.
复制标题
DOI：
10.2967/jnumed.115.157982
复制
发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Caravan P
中科院分区：
文献类型：
--
作者：
Blasi F;Oliveira BL;Rietz TA;Rotile NJ;Day H;Naha PC;Cormode DP;Izquierdo-Garcia D;Catana C;Caravan P
尽管当前的血栓成像方式和新的诊断算法取得了进展，但深静脉血栓栓塞性疾病的诊断仍然具有挑战性。我们最近报道了新型纤维蛋白特异性正电子发射断层扫描探针 64Cu-FBP8 的高靶标摄取和血栓成像功效。在这里，我们测试了 64Cu-FBP8-PET 检测深静脉血栓和肺栓塞 (DVT-PE) 后血栓源和罪魁祸首的可行性。为了支持 64Cu-FBP8 的临床转化，我们利用大鼠体内时间依赖性生物分布进行了人体剂量测定估计。 Sprague-Dawley 大鼠（n=7）在股静脉上应用氯化铁以引发血栓形成。深静脉血栓形成后 30 分钟或 2 天，通过颈内注射用 125 I-纤维蛋白原标记的预制血凝块诱导肺栓塞。进行 PET 成像来检测血栓，并使用单光子发射断层扫描 (SPECT) 来确认体内肺栓塞的位置。使用离体伽玛计数和组织病理学来验证成像结果。在施用 64Cu-FBP8 后的不同时间点对健康大鼠 (n=30) 进行详细的生物分布，以估计人体辐射剂量。给予 64Cu-FBP8 后进行纵向全身 PET/MR 成像 (n=2)，以进一步评估放射性清除率。 64Cu-FBP8-PET 成像检测 DVT-PE 后肺栓塞和静脉血栓的位置，显示目标组织和背景组织之间的摄取存在显着差异（P<0.001）。体内 SPECT 成像和离体伽马计数证实了肺栓塞的位置。静脉血栓的 PET 定量显示，较年轻的血栓中的探针摄取量高于较老的血栓，这一结果经离体分析证实（P<0.001）。组织病理学显示血栓纤维蛋白含量随年龄而减少（P=0.006），进一步支持了影像学发现。生物分布和全身 PET/MR 成像显示 64Cu-FBP8 的身体快速清除（主要是肾脏清除）。男性有效剂量估计为 0.021 mSv/MBq，女性有效剂量为 0.027 mSv/MBq，支持在人体试验中使用 64Cu-FBP8 的可行性。我们证明 64Cu-FBP8-PET 是一种可行的 DVT-PE 成像方法，并且放射性对健康的不良影响不应限制 64Cu-FBP8 的临床转化。
The diagnosis of deep venous thromboembolic disease is still challenging despite the progress of current thrombus imaging modalities and new diagnostic algorithms. We recently reported the high target uptake and thrombus imaging efficacy of the novel fibrin-specific positron emission tomography probe 64Cu-FBP8. Here, we tested the feasibility of 64Cu-FBP8-PET to detect source thrombi and culprit emboli after deep vein thrombosis and pulmonary embolism (DVT-PE). To support clinical translation of 64Cu-FBP8, we performed a human dosimetry estimation using time-dependent biodistribution in rats. Sprague-Dawley rats (n=7) underwent ferric chloride application on the femoral vein to trigger thrombosis. Pulmonary embolism was induced 30 min or 2 days after deep vein thrombosis by intrajugular injection of a preformed blood clot labeled with 125I-Fibrinogen. PET imaging was performed to detect the clots, and single-photon emission tomography (SPECT) was used to confirm in vivo the location of the pulmonary emboli. Ex vivo gamma-counting and histopathology were used to validate the imaging findings. Detailed biodistribution was performed in healthy rats (n=30) at different time-points after 64Cu-FBP8 administration to estimate human radiation dosimetry. Longitudinal whole-body PET/MR imaging (n=2) was performed after 64Cu-FBP8 administration to further assess radioactivity clearance. 64Cu-FBP8-PET imaging detected the location of lung emboli and venous thrombi after DVT-PE, revealing significant differences in uptake between target and background tissues (P<0.001). In vivo SPECT imaging and ex vivo gamma-counting confirmed the location of the lung emboli. PET quantification of the venous thrombi revealed that probe uptake was greater in younger clots than in older ones, a result confirmed by ex vivo analyses (P<0.001). Histopathology revealed an age-dependent reduction of thrombus fibrin content (P=0.006), further supporting the imaging findings. Biodistribution and whole-body PET/MR imaging showed rapid, primarily renal, body clearance of 64Cu-FBP8. The effective dose was estimated to be 0.021 mSv/MBq for male and 0.027 mSv/MBq for female, supporting the feasibility of using 64Cu-FBP8 in human trials. We showed that 64Cu-FBP8-PET is a feasible approach to image DVT-PE, and that radiogenic adverse health effects should not limit the clinical translation of 64Cu-FBP8.