Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with ¹⁸F-Al labeled Cys³⁹-exendin-4

Purpose: Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, ¹⁸F-Al labeled exendin-4 analog, ¹⁸F-Al-NOTA-MAL-Cys³⁹-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. Methods: The targeting of ¹⁸F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with ¹⁸F-Al-NOTA-MAL-Cys³⁹-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. Results: The pancreas of healthy rats was readily visualized after administration of ¹⁸F-Al-NOTA-MAL-Cys³⁹-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 ± 0.15%ID/g and 0.23 ± 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 ± 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. Conclusion: The favorable preclinical data indicated that ¹⁸F-Al-NOTA-MAL-Cys³⁹-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells.