Synthesis and preclinical evaluation of a novel PET/fluorescence dual-modality probe targeting fibroblast activation protein

Bioorg Chem. 2024 May:146:107275. doi: 10.1016/j.bioorg.2024.107275. Epub 2024 Mar 13.

Abstract

Early diagnosis and precise surgical intervention are crucial for cancer patients. We aimed to develop a novel positron emission tomography (PET)/fluorescence dual-modality probe for preoperative diagnosis, intraoperative guidance, and postoperative monitoring of fibroblast activation protein (FAP)-positive tumors. FAPI-FAM was synthesized and labeled with gallium-68. [68Ga]Ga-FAPI-FAM showed favorable in vivo and in vitro characteristics, specific binding affinity, and excellent tumor accumulation in FAP-positive cells and mice xenografts. Excellent tumor-to-background contrast was found owing to high tumor uptake, prolonged retention, and rapid renal clearance of [68Ga]Ga-FAPI-FAM. Moreover, a specific fluorescence signal was detected in FAP-positive tumors during ex vivo fluorescence imaging, demonstrating the feasibility of whole-body tumor detection and intraoperative tumor delineation.

Keywords: Dual-modality imaging; Fibroblast activation protein; Fluorescence imaging; Gallium-68; Positron emission tomography.

MeSH terms

  • Animals
  • Fibroblasts / metabolism
  • Fluorescence
  • Gallium Radioisotopes
  • Humans
  • Mice
  • Neoplasms* / metabolism
  • Positron-Emission Tomography / methods
  • Quinolines*

Substances

  • Gallium Radioisotopes
  • Quinolines