68Ga-Labeled 3PRGD2 for Dual PET and Cerenkov Luminescence Imaging of Orthotopic Human Glioblastoma
68Ga-Labeled 3PRGD2 for Dual PET and Cerenkov Luminescence Imaging of Orthotopic Human Glioblastoma
复制标题
(68)Ga 标记的 3PRGD2，用于原位人胶质母细胞瘤的双重 PET 和切伦科夫发光成像。
DOI：
10.1021/acs.bioconjchem.5b00169
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发表时间：
2015-06-01
影响因子：
4.7
通讯作者：
Wang, Fan
中科院分区：
文献类型：
--
作者：
Fan, Di;Zhang, Xin;Wang, Fan
β-发射器可以产生切伦科夫辐射，可通过切伦科夫发光成像（CLI）检测，允许PET和CLI与一种放射性示踪剂组合，用于肿瘤诊断和手术期间的视觉引导。最近，临床可行性CLI与既定的治疗试剂（NaI）-I-131和PET示踪剂F-18-FDG被证明。Ga-68具有比F-18和I-131更高的切伦科夫光输出，这将导致更高的CLI灵敏度，并改善CLI在临床应用中的结果。然而，基于Ga-68的肿瘤特异性示踪剂用于CLI的研究有限。在这项研究中，我们检查了Ga-68-放射性标记的DOTA-3PRGD 2（Ga-68 - 3PRGD（2））用于原位U87 MG人胶质母细胞瘤的双重PET和CLI的用途。为此，用IVIS光谱系统（PerkinElmer，USA）测量Ga-68和F-18的切伦科夫效率。Ga-68的CLI信号强度比F-18强15倍。在U87 MG人胶质母细胞瘤异种移植物中进行Ga-68 - 3PRGD（2）的PET和CLI。PET和CLI均显示在注射后1小时，Ga-68 - 3PRGD（2）在U87 MG人胶质母细胞瘤异种移植物中显著积累。与F-18-FDG相比，其大脑中的背景极低。此外，Ga-68 - 3PRGD（2）用于原位人胶质母细胞瘤的双重PET和CLI。原位人胶质母细胞瘤清晰可视化的两种成像方式。此外，在正常小鼠中评估Ga-68 - 3PRGD（2）的生物分布以估计辐射剂量。全身有效剂量为20.1 +/-3.3 mu Sv/MBq，相当于每次全身PET扫描3.7 mSv，注射剂量为5 mCi。因此，与F-18-FDG（7.0 mSv）相比，Ga-68 - 3PRGD（2）对患者的辐射暴露较少。Ga-68 - 3PRGD（2）在双重PET和CLI中的使用显示了肿瘤诊断和图像引导手术的巨大前景。
beta-Emitters can produce Cerenkov radiation that is detectable by Cerenkov luminescence imaging (CLI), allowing the combination of PET and CLI with one radiotracer for both tumor diagnosis and visual guidance during surgery. Recently, the clinical feasibility of CLI with the established therapeutic reagent (NaI)-I-131 and the PET tracer F-18-FDG was demonstrated. Ga-68 possesses a higher Cerenkov light output than F-18 and I-131, which would result in higher sensitivity for CLI and improve the outcome of CLI in clinical applications. However, the research on Ga-68-based tumor-specific tracers for CLI is limited. In this study, we examined the use of Ga-68-radiolabeled DOTA-3PRGD2 (Ga-68-3PRGD(2)) for dual PET and CLI of orthotopic U87MG human glioblastoma. For this purpose, the Cerenkov efficiencies of Ga-68 and F-18 were measured with the IVIS Spectrum system (PerkinElmer, USA). The CLI signal intensity of Ga-68 was 15 times stronger than that of F-18. PET and CLI of Ga-68-3PRGD(2) were performed in U87MG human glioblastoma xenografts. Both PET and CLI revealed a remarkable accumulation of Ga-68-3PRGD(2) in the U87MG human glioblastoma xenografts at 1 h p.i. with an extremely low background in the brain when compared with F-18-FDG. Furthermore, Ga-68-3PRGD(2) was used for dual PET and CLI of orthotopic human glioblastoma. The orthotopic human glioblastoma was clearly visualized by both imaging modalities. In addition, the biodistribution of Ga-68-3PRGD(2) was assessed in normal mice to estimate the radiation dosimetry. The whole-body effective dose is 20.1 +/- 3.3 mu Sv/MBq, which is equal to 3.7 mSv per whole-body PET scan with a 5 mCi injection dose. Thus, Ga-68-3PRGD(2) involves less radiation exposure in patients when compared with F-18-FDG (7.0 mSv). The use of Ga-68-3PRGD(2) in dual PET and CLI shows great promise for tumor diagnosis and image-guided surgery.