Radical resection is the most effective method for malignant
tumor treatments. However, conventional imaging cannot fully satisfy the clinical needs of
surgical navigation. This study presents a novel triple-modality positron emission tomography (PET)-Cerenkov radiation energy transfer (CRET)-confocal
laser endomicroscopy (CLE) imaging strategy for intraoperative
tumor imaging and
surgical navigation. Using clinical
radiopharmaceuticals and
fluorescein sodium (FS), this strategy can accurately detect the
tumor and guide the
tumor surgery. The FS emission property under Cerenkov radiation excitation is investigated using 2-deoxy-2-18F-fluoroglucose and 11C-choline. Performances of the PET-CRET-CLE imaging and the CRET-CLE
image-guided surgery are evaluated on mouse models. The CRET signal at 8 mm depth is stronger than the Cerenkov luminescence at 1 mm depth in phantoms. In vivo experiments indicate that 0.5 mL kg-1 of 10% FS generates the strongest CRET signal, which can be observed immediately after FS injection. A
surgical navigation study shows that the
tumors are precisely detected and resected using intraoperative CRET-CLE. In summary, a PET-CRET-CLE triple-modality imaging strategy is developed. This strategy can detect the
tumors and precisely guide the
tumor resection using clinical pharmaceuticals. This triple-modality imaging shows high potential in
surgical navigation research and clinical translation.