18F-Labeled Amidobenzimidazole Analogue for Visualizing STING Expression in Tumor

Mol Pharm. 2024 Apr 1;21(4):1942-1951. doi: 10.1021/acs.molpharmaceut.3c01201. Epub 2024 Mar 6.

Abstract

The stimulator of interferon genes (STING) is pivotal in mediating STING-dependent type I interferon production, which is crucial for enhancing tumor rejection. Visualizing STING within the tumor microenvironment is valuable for STING-related treatments, yet the availability of suitable STING imaging probes is limited. In this study, we developed [18F]AlF-ABI, a novel 18F-labeled agent featuring an amidobenzimidazole core structure, for positron emission tomography (PET) imaging of STING in B16F10 and CT26 tumors. [18F]AlF-ABI was synthesized with a decay-corrected radiochemical yield of 38.0 ± 7.9% and radiochemical purity exceeding 97%. The probe exhibited a nanomolar STING binding affinity (KD = 35.6 nM). Upon administration, [18F]AlF-ABI rapidly accumulated at tumor sites, demonstrating significantly higher uptake in B16F10 tumors compared to CT26 tumors, consistent with STING immunofluorescence patterns. Specificity was further validated through in vitro cell experiments and in vivo blocking PET imaging. These findings suggest that [18F]AlF-ABI holds promise as an effective agent for visualizing STING in the tumor microenvironment.

Keywords: PET imaging; amidobenzimidazole analogue; monomer; stimulator of interferon genes; tumor microenvironment.

MeSH terms

  • Benzimidazoles* / chemistry
  • Benzimidazoles* / pharmacology
  • Cell Line, Tumor
  • Fluorine Radioisotopes*
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Neoplasms / diagnostic imaging
  • Neoplasms / metabolism
  • Positron-Emission Tomography* / methods
  • Radiopharmaceuticals / chemistry
  • Tumor Microenvironment*

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Benzimidazoles
  • STING1 protein, human
  • Membrane Proteins