Dual-modality imaging and quantification of GLP-1R positive insulinoma and pancreatic beta-cell mass using a bimodal PET/fluorescence exendin-4 peptide

Objectives GLP1-R targeting with exendin based peptides has shown promise for imaging of insulinomas and assessing pancreatic beta-cell mass (1,2). A dual-modality (nuclear and optical) GLP-1 ligand provides the opportunity to study GLP-1R expressing cells at the whole body level with PET and at high resolutions with optical imaging.

Methods A novel sequential one-pot synthesis (radiolabeling/click reaction) is the key step in the synthesis of the multimodal imaging agent which is based on exendin-4, the chelator sarcophagine for labeling with radiometals, and a NIR fluorescent dye for optical imaging. Transgenic mice with beta-cell specific expression of EGFP and 916-1 insulinoma xenografts were used to demonstrate specificity.

Results With new radiolabeling and click chemistry conditions we were able to synthesize a dual-modality imaging agent and radiolabel it with 64Cu (RCY = >95%, specific activity: 396 μCi/μg). The ligand visualized small (< 2 mm) xenografts at 1 h p.i. Targeting of pancreatic islets was demonstrated by PET and autoradiography. Fluorescence microscopy of pancreatic sections demonstrated excellent co-localization of EGFP and NIR fluorescence, confirming specific binding to GLP-1R.

Conclusions We have synthesized and characterized a new bimodal imaging agent that may be useful for pre-/and intraoperative imaging of insulinomas. Our results also demonstrate that optical imaging with a dual-modality probe can confirm specific targeting of a PET tracer at the cellular level.

Research Support Supported by the Brain Tumor Center and the Imaging and Radiation Sciences Program of MSKCC (TR).