Abstract
1050
Purpose: IGF-1R has an important role in cell mitosis, survival, and transformation [1-2]. 68Ga-NOTA-ZIGF-1R:4:40, a new IGF-1R targeted probe was synthesized and evaluated in lung cancer.
Methods: 68Ga-NOTA-ZIGF-1R:4:40 was synthesized by a Gallium generator. IGF-1R high expression, moderate expression, and low expression lung cancer cell lines were filtered from H1299, H520, and, H460 cell lines by immunofluorescence and western blot in cell level and tumor organizational level . According to the results, cell uptake and efflux were evaluated, and tumor nude mouse model were constructed. PET/CT imaging was undergone in 1h and 2h after the new probe was injected. The images were analyzed with GE AW 4.6 workstation.
Results: H1299, H520 and H460 were filtered as the high expression, moderate expression, and low expression IGF-1R lung cancer cell lines, respectively.68Ga-NOTA-ZIGF-1R:4:40had significantly higher cell uptake in H1299 cellsthan in H520 and H460 cells. H520 was between those of H1299 and H460 with moderate cell uptake of68Ga-NOTA-ZIGF-1R:4:40uptake in vitro experiments. In PET/CT images, 68Ga-NOTA-ZIGF-1R:4:40 was accumulated in different lung cancer models with different levels. The maximum uptake was found in H1299 tumor-bearing nude mice, the second was H520 tumor-bearing nude mice, and the least was H460 tumor-bearing nude mice, which was consistent with IGF-1R expression confirmed by immunofluorescence and western blot.
Conclusions: New IGF-1R targeted probe,68Ga-NOTA-ZIGF-1R:4:40, was synthesized successfully. And it could distinguish different IGF-1R expression levels, which was expected to guide IGF-1R targeted therapy and evaluate treatment efficacy in real time noninvasively.A large number of verification experiments were still needed to be studied. REFERENCE: [1] Coppola D, Ferber A, Miura M, et al. A functional insulin-like growth factor I receptor is required for the mitogenic and transforming activities of the epidermal growth factor receptor. Mol Cell Biol. 1994;14(7):4588-4595. [2] Baserga R. The insulin-like growth factor-I receptor as a target for cancer therapy. Expert Opin Ther Targets. 2005;9(4):753-76. [3] Hye-Young Min, Hye Jeong Yun, Ji-Sun Lee, et al. Targeting the insulin-like growth factor receptor and Src signaling network for the treatment of non-small cell lung cancer Mol Cancer. 2015; 14: 113.