Synthesis and evaluation of 18F-PTTCO-Cys40-Exendin-4 for PET imaging of ectopic insulinomas in rodents

Bioorg Chem. 2020 May:98:103718. doi: 10.1016/j.bioorg.2020.103718. Epub 2020 Mar 5.

Abstract

A major limitation in the development of radiolabeled Exendin-4 analogues (short half-life isotopes) is an inability to efficiently and rapidly separate final products from precursors. This is important as lack of purity in the final product decreases probe efficiency. The purpose of this study was to develop a method to prepare the high-purity imaging reagent [18F] PTTCO-Cys40-Exendin-4. To accomplish this, magnetic TCO-beads were incubated with the crude product to remove unlabeled Exendin-4. In rodents pre-treatment with purified [18F] PTTCO-Cys40-Exendin-4 (~1.85 MBq) allowed precise microPET imaging of ectopic insulinomas. Moreover, analogue uptake was successfully blocked by administering non-labelled "cold" Exendin-4. Biodistribution data revealed that [18F] PTTCO-Cys40-Exendin-4 accumulated specifically in GLP-1R-enriched insulinomas in mice, confirming results obtained using miroPET. Investigation of [18F] PTTCO-Cys40-Exendin-4 as a tracer to image portal vein-transplanted pancreatic islets is proceeding in animals.

Keywords: (18)F-Exendin-4; Glucagon-like peptide receptors; INS-1; Insulinoma; Pancreatic islet transplantation; Positron emission tomography (PET).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Contrast Media / chemical synthesis
  • Contrast Media / chemistry*
  • Dose-Response Relationship, Drug
  • Fluorine Radioisotopes
  • Insulinoma / diagnostic imaging*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Molecular Structure
  • Neoplasms, Experimental / diagnostic imaging
  • Pancreatic Neoplasms / diagnostic imaging*
  • Positron-Emission Tomography*
  • Rats
  • Structure-Activity Relationship

Substances

  • Contrast Media
  • Fluorine Radioisotopes