Specific molecular imaging of BALB/c model mice with Graves' ophthalmopathy based on high expression of insulin-like growth factor 1 receptor.

Abstract

Objective: At present, most of the targeted imaging based on insulin-like growth factor 1 receptor (IGF-1R) is for tumor research, and there is no IGF-1R-targeted imaging for Graves' ophthalmopathy(GO). This study aims to develop a peptide probe, ^99mTc-Z_IGF1R:4551-GGGC, targeting the IGF-1R, and to achieve specific imaging in Graves' disease (GD) animal models exhibiting GO.

Methods: 99mTc-ZIGF1R:4551-GGGC probe was synthesized using a direct labeling method and its labeling efficiency assessed via instant thin-layer chromatography (ITLC). Western blot analysis confirmed the overexpression of IGF-1R in malignant melanoma B16F10 cells. Subsequent SPECT/CT whole-body imaging of B16F10 tumor-bearing mice evaluated the probe's targeting accuracy. In addition, a GO model was established using an electroporation immunoassay, followed by serological and histopathological examinations. The GO models then underwent 99mTc-ZIGF1R:4551-GGGC SPECT/CT imaging to assess eye-targeted imaging capabilities.

Results: The peptide probe exhibited a labeling efficiency exceeding 90%. Both GD and GO models were effectively created via electroporation immunoassay. Imaging results indicated significant accumulation and retention of the peptide probes in the tumors of B16F10 tumor-bearing mice. In the GO models, probe uptake was predominantly observed in retrobulbar tissues, contrasting with primary accumulation in the lungs and gastrointestinal tract in normal mice, where only minimal tracer was observed in retrobulbar tissues. Notably, GO mice demonstrated higher probe uptake and prolonged retention.

Conclusion: This study successfully established GD and GO models, reducing the duration of the immune cycle. Moreover, a peptide probe targeting IGF-1R was synthesized, enabling specific imaging of retrobulbar tissues in GO models.