⁶⁸Ga-Labeled 3PRGD₂ for Dual PET and Cerenkov Luminescence Imaging of Orthotopic Human Glioblastoma

β-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 Na¹³¹I and the PET tracer ¹⁸F-FDG was demonstrated. ⁶⁸Ga possesses a higher Cerenkov light output than ¹⁸F and ¹³¹I, which would result in higher sensitivity for CLI and improve the outcome of CLI in clinical applications. However, the research on ⁶⁸Ga-based tumor-specific tracers for CLI is limited. In this study, we examined the use of ⁶⁸Ga-radiolabeled DOTA-3PRGD₂ (⁶⁸Ga-3PRGD₂) for dual PET and CLI of orthotopic U87MG human glioblastoma. For this purpose, the Cerenkov efficiencies of ⁶⁸Ga and ¹⁸F were measured with the IVIS Spectrum system (PerkinElmer, USA). The CLI signal intensity of ⁶⁸Ga was 15 times stronger than that of ¹⁸F. PET and CLI of ⁶⁸Ga-3PRGD₂ were performed in U87MG human glioblastoma xenografts. Both PET and CLI revealed a remarkable accumulation of ⁶⁸Ga-3PRGD₂ in the U87MG human glioblastoma xenografts at 1 h p.i. with an extremely low background in the brain when compared with ¹⁸F-FDG. Furthermore, ⁶⁸Ga-3PRGD₂ 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 ⁶⁸Ga-3PRGD₂ was assessed in normal mice to estimate the radiation dosimetry. The whole-body effective dose is 20.1 ± 3.3 μSv/MBq, which is equal to 3.7 mSv per whole-body PET scan with a 5 mCi injection dose. Thus, ⁶⁸Ga-3PRGD₂ involves less radiation exposure in patients when compared with ¹⁸F-FDG (7.0 mSv). The use of ⁶⁸Ga-3PRGD₂ in dual PET and CLI shows great promise for tumor diagnosis and image-guided surgery