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

## TL;DR

This study develops a new imaging probe targeting IGF-1R to visualize Graves’ ophthalmopathy in mice, showing specific accumulation in affected eye tissues.

## Contribution

A novel IGF-1R-targeted peptide probe is synthesized and validated for specific imaging of Graves’ ophthalmopathy in animal models.

## Key findings

- The peptide probe 99mTc-ZIGF1R:4551-GGGC showed over 90% labeling efficiency and targeted IGF-1R in tumor-bearing mice.
- In Graves’ ophthalmopathy models, the probe accumulated in retrobulbar tissues, unlike in normal mice.
- The study established efficient GD and GO models with reduced immune cycle duration.

## Abstract

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-ZIGF1R:4551-GGGC, targeting the IGF-1R, and to achieve specific imaging in Graves’ disease (GD) animal models exhibiting GO.

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.

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.

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.