Cerenkov luminescence imaging (CLI) is a novel optical imaging technique that has been applied in clinic using various
radionuclides and
radiopharmaceuticals. However, clinical application of CLI has been limited by weak optical signal and restricted tissue penetration depth. Various
fluorescent probes have been combined with
radiopharmaceuticals for improved imaging performances. However, as most of these probes only interact with Cerenkov luminescence (CL), the low photon fluence of CL greatly restricted it's interaction with
fluorescent probes for in vivo imaging. Therefore, it is important to develop probes that can effectively convert energy beyond CL such as β and γ to the low energy optical signals. In this study, a Eu3+ doped
gadolinium oxide (Gd2O3:Eu) was synthesized and combined with
radiopharmaceuticals to achieve a red-shifted optical spectrum with less tissue scattering and enhanced optical signal intensity in this study. The interaction between Gd2O3:Eu and
radiopharmaceutical were investigated using 18F-fluorodeoxyglucose (18F-FDG). The ex vivo optical signal intensity of the mixture of Gd2O3:Eu and
18F-FDG reached 369 times as high as that of CLI using
18F-FDG alone. To achieve improved biocompatibility, the Gd2O3:Eu nanoparticles were then modified with
polyvinyl alcohol (PVA), and the resulted nanoprobe PVA modified Gd2O3:Eu (Gd2O3:Eu@PVA) was applied in intraoperative
tumor imaging. Compared with
18F-FDG alone, intraoperative administration of Gd2O3:Eu@PVA and
18F-FDG combination achieved a much higher
tumor-to-normal tissue ratio (TNR, 10.24 ± 2.24 vs. 1.87 ± 0.73, P = 0.0030). The use of Gd2O3:Eu@PVA and
18F-FDG also assisted intraoperative detection of
tumors that were omitted by preoperative positron emission tomography (PET) imaging. Further experiment of
image-guided surgery demonstrated feasibility of image-guided
tumor resection using Gd2O3:Eu@PVA and
18F-FDG. In summary, Gd2O3:Eu can achieve significantly optimized imaging property when combined with
18F-FDG in intraoperative
tumor imaging and image-guided
tumor resection surgery. It is expected that the development of the Gd2O3:Eu nanoparticle will promote investigation and application of novel nanoparticles that can interact with
radiopharmaceuticals for improved imaging properties. This work highlighted the impact of the nanoprobe that can be excited by
radiopharmaceuticals emitting CL, β, and γ radiation for precisely imaging of
tumor and intraoperatively guide
tumor resection.