Abstract
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.
Highlights
Cerenkov luminescence imaging (CLI) is an emerging optical imaging modality based on the Cerenkov radiation that can be generated by a variety of radionuclides such as 18F, 11C, 64Cu, 131I, 177Lu, etc., and it has been successfully applied for the image-guided cancer surgery in small animal models.[21,22]
The quantification analysis results indicated that the Cerenkov radiation energy transfer (CRET) signal intensity of the mixture (18FFDG and 0.05% fluorescein sodium (FS)) was ≈6.8-folds of that of CLI signal intensity of 18F-FDG (Figure 1c, 2.97 ± 0.84 vs 0.44 ± 0.06 × 106 p s−1 cm−2 sr−1)
As an important strategy, using molecular imaging techniques for surgical navigation can provide valuable assistances to improve the surgical performances with high potential for clinical translation.[10–13]
Summary
Malignant tumors such as hepatocellular carcinoma (HCC), breast cancer, glioblastoma, and lung cancer are important causes of human death.[1–3] Radical resection is of great significance to the prognosis of these malignant tumors in patients.[4–6] tumors are difficult to be completely resected during the surgery since the irregular shape and indistinct margins of the tumors.[7,8] For example, during the HCC surgery, tumor resection area determined mainly depends on the inspection and palpation of the surgeons, which may lead to omission of residual tumors or unnecessary removal of normal tissues.[9,10] Inaccuracy of the tumor resection can seriously affect prognosis and life quality of HCC patients.[11,12] Aiming to improve the HCC resection precision, a wide variety of molecular imaging techniques have been explored to visualize tumor margin and guide the surgery.[13,14] High-sensitivity. Cerenkov luminescence imaging (CLI) is an emerging optical imaging modality based on the Cerenkov radiation that can be generated by a variety of radionuclides such as 18F, 11C, 64Cu, 131I, 177Lu, etc., and it has been successfully applied for the image-guided cancer surgery in small animal models.[21,22]. As a macroscopic imaging modality, CRET can locate tumors in living subjects, but light scattering limits the imaging resolution, which makes CRET difficult to precisely delineate the tumor boundaries.[31] To overcome this problem, we plan to combine confocal laser endomicroscopy (CLE), which is a new type of microscopic imaging based on the principle of tissue reflectance or tissue fluorescence.[32]. To the best of our knowledge, this is the first study to use radiopharmaceuticals and fluorescein sodium as a triple-modality surgical navigation strategy, and it allows us to successfully combine PET, CRET, and CLE imaging to achieve precise tumor surgery
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