The development of PET/MRI dual modality probe based on IO nanoparticle for pancreatic beta-cell imaging

Objectives Although there is a growing unmet need to noninvasively image and quantify the mass of pancreatic beta-cells, beta-cells imaging is very challenging due to their low abundance in the pancreas. Recent advances in this area include the application of various molecular imaging techniques, such as MRI and PET. However, each modality has its own advantages and disadvantages. In this report, we developed a PET/MRI dual modality imaging probe targeting glucagon-like peptide 1 receptor (GLP-1R) for pancreatic beta-cell imaging.

Methods The amino functionalized iron oxide (IO) nanoparticle was reacted with DOTA-NHS or AmBaSar for ⁶⁴Cu labeling. The in vitro stability was tested for ⁶⁴Cu-DOTA-IO and ⁶⁴Cu-AmBaSar-IO. AmBaSar-IO-Exendin-4 was constructed by conjugating C-Cys-Exendin-4 with IO through NHS-PEG-MAL. The receptor binding affinity was determined by in vitro cell binding assays with Insulinoma cells (INS-1) and microPET imaging was performed on xenograft INS-1 tumor models.

Results We have successfully obtained ⁶⁴Cu-labeled DOTA-IO, AmBaSar-IO and AmBaSar-IO-Exendin-4 in 65-70% yield at standard labeling condition. In vitro stability study showed that the radiochemical purity of ⁶⁴Cu-DOTA-IO was only 40% at 1 h after purification compared with 90% for ⁶⁴Cu-AmBaSar-IO. The cell binding assay demonstrated that AmBaSar-IO-Exendin-4 (IC₅₀ = 12.8 ± 0.6 pmol) had much higher binding affinity than Exendin-4 (IC₅₀ = 520.1 ± 11.2 pmol). The tumor uptake for ⁶⁴Cu-AmBaSar-IO-Exenidn-4 could be partially blocked by cold Exendin-4.

Conclusions In this research, we have developed a PET/MRI dual modality imaging probe targeting GLP-1R. This nanoparticle based probe could be labeled with ⁶⁴Cu with good yield and demonstrated a high binding affinity to GLP-1R in vitro. The further modification will be needed for islets imaging.

Research Support This work was supported by a grant from the Juvenile Diabetes Research Foundation International