Nanoparticle-mediated radiopharmaceutical-excited fluorescence molecular imaging allows precise image-guided tumor-removal surgery.

Fluorescent molecular imaging technique has been actively explored for optical image-guided cancer surgery in pre-clinical and clinical research and has attracted many attentions. However, the efficacy of the fluorescent image-guided cancer surgery can be compromised by the low signal-to-noise ratio caused by the external light excitation. This study presents a novel nanoparticle-mediated radiopharmaceutical-excited fluorescent (REF) image-guided cancer surgery strategy, which employs the internal dual-excitation of europium oxide nanoparticles through both gamma rays and Cerenkov luminescence emitted from radiopharmaceuticals. The performance of the novel image-guided surgery technique was systematically evaluated using subcutaneous breast cancer 4 T1 tumor models, orthotropic and orthotropic-ectopic hepatocellular carcinoma tumor-bearing mice. The results reveal that the novel REF image-guided cancer surgery technique exhibits high performance of detecting invisible ultra-small size tumor (even less than 1 mm) and residual tumor tissue. Our study demonstrates the high potential of the novel image-guided cancer surgery for precise tumor resection.