Insulin-Like Growth Factor-1 Receptor Targeted Fluorescent Imaging for Gallbladder Cancer in Orthotopic Mouse Models

Abstract

Background/Aims: Gallbladder cancer is fatal, but fluorescent imaging technology can facilitate timely diagnosis and improve patient outcomes. Fluorophore-conjugated insulin-like growth factor-1 receptor (IGF-1R) targeted antibodies were used to visualize gallbladder cancer in orthotopic tumor mouse models.Methods: Western blotting, flow cytometric analysis, and confocal microscopy detected the expression of IGF-1R in SNU-308, SNU-478, and SNU-1196 bile duct cancer cells. In vivo imaging of SNU-478 and SNU-1196 subcutaneous tumors and orthotopic gallbladder tumor models of SNU-478 were performed after injection with DyLight 650-conjugated IGF-1R antibody.Results: Western blotting and flow cytometric analysis showed that IGF-1R was expressed in bile duct cancer cells, and confocal microscopy demonstrated that IGF-1R antibody was able to bind to IGF-1R on the cell membrane. Fluorescent IGF-1R antibody injected into the mouse tail vein made subcutaneous tumors and orthotopic tumors become fluorescent. The intensity of fluorescence from the tumor was stronger than that from surrounding normal tissues. Histochemical examination confirmed that the tumor was located inside the gallbladder and adjacent liver parenchyma of mice. Conclusions:Our study showed that a fluorescent IGF-1R-targeted antibody could help detect gallbladder tumors. Tumor-specific imaging technology can be applied to endoscopy, laparoscopy, and robotic surgery for better management of gallbladder cancer.

Interlinking of diabetes mellitus and cancer: An overview

“…22,23 Insulin receptor-A and IGF-1 receptor are found in fetal tissues and cancer cells, respectively. 24 It is well known that other factors and proteins produced centrally and indirectly may influence the release of growth hormone (GH). 25 Through long-loop negative feedback, IGF-1 may also function to regulate pituitary GH output at the hypothalamus level.…”

“…High glucose, can boost hepatic production of insulin and IGF‐1, which subsequently activates the insulin and IGF‐1 receptor, and encourages cell proliferation 22,23 . Insulin receptor‐A and IGF‐1 receptor are found in fetal tissues and cancer cells, respectively 24 …”