van Mourik Tiemen R, Claesener Michael, Nicolay Klaas, Grüll Holger
Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Department of Nuclear Medicine, University of Münster, Münster, Germany.
J Labelled Comp Radiopharm. 2017 May 30;60(6):286-293. doi: 10.1002/jlcr.3501.
Fibrin deposition is observed in several diseases such as atherosclerosis, deep vein thrombosis, and also tumors, where it contributes to the formation of mature tumor stroma. The aim of this study was to develop a gallium-labeled peptide tracer on the basis of the fibrin-targeting peptide Epep for PET imaging of fibrin deposition. For this purpose, the peptide Epep was modified with a NOTA moiety for radiolabeling with Ga and Ga and compared with the earlier validated In-DOTA-Epep tracer. In vitro binding assays of Ga-NOTA-Epep displayed an enhanced retention as compared to previously published data showing binding of In-DOTA-Epep to human (84.0 ± 0.6 vs 66.6 ± 1.4 %Dose) and mouse derived fibrin clots (83.5 ± 1.7 vs 74.2 ± 2.4% Dose). In vivo blood kinetics displayed a bi-phasic elimination profile (t , = 2.6 ± 1.0 minutes and t , = 15.8 ± 1.3 minutes) and ex vivo biodistribution showed low blood values at 4 hours post injection and a low uptake in nontarget tissue (<0.2 %ID/g; kidneys, 1.9%ID/g). In conclusion, taking into account the ease of radiolabeling and the promising in vitro and in vivo studies, gallium-labeled Epep displays the potential for further development towards a PET tracer for fibrin deposition.
在动脉粥样硬化、深静脉血栓形成等多种疾病以及肿瘤中都观察到了纤维蛋白沉积，它有助于成熟肿瘤基质的形成。本研究的目的是基于靶向纤维蛋白的肽Epep开发一种镓标记的肽示踪剂，用于纤维蛋白沉积的PET成像。为此，用NOTA部分修饰肽Epep以用镓和镓进行放射性标记，并与先前验证的铟-DOTA-Epep示踪剂进行比较。与先前发表的显示铟-DOTA-Epep与人源（84.0±0.6对66.6±1.4%Dose）和小鼠源纤维蛋白凝块（83.5±1.7对74.2±2.4%Dose）结合的数据相比，镓-NOTA-Epep的体外结合试验显示出保留增强。体内血液动力学显示出双相消除曲线（t，=2.6±1.0分钟和t，=15.8±1.3分钟），体外生物分布显示注射后4小时血液值较低，非靶组织摄取较低（<0.2%ID/g；肾脏，1.9%ID/g）。总之，考虑到放射性标记的简便性以及有前景的体外和体内研究，镓标记的Epep显示出进一步开发用于纤维蛋白沉积的PET示踪剂的潜力。
