Ga-68-Labeled 3PRGD(2) for Dual PET and Cerenkov Luminescence Imaging of Orthotopic Human Glioblastoma

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.National Natural Science Foundation of China (NSFC) [81125011, 81321003, 81420108019, 81427802, 81201127]; Beijing Natural Science Foundation [7142086]SCI(E)ARTICLEshijiyun@moon.ibp.ac.cn; wangfan@bjmu.edu.cn61054-10602