Radiosynthesis and in-vitro identification of a molecular probe 131I-FAPI targeting cancer-associated fibroblasts

Yaxin Tian1,2, Yanghongyan Jiang3, Ping Ma1

  • 1Department of Nuclear Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.

Frontiers in Oncology
|September 16, 2024
PubMed
Abstract

Insights

A novel radioactive tracer, 131I-FAPI, effectively targets cancer cells in vitro. This fibroblast activation protein inhibitor shows promise for cancer diagnosis and therapy by inhibiting tumor cell proliferation and migration.

Area of Science:

  • Nuclear Medicine
  • Radiochemistry
  • Oncology

Background:

  • Fibroblast activation protein (FAP) is a key marker overexpressed in various malignant epithelial tumors but minimally in healthy tissues.
  • FAP inhibitors (FAPI) are crucial for targeted cancer diagnosis and therapy due to their specific binding to FAP.
  • Developing novel radiolabeled FAPI probes enhances their utility in molecular imaging and therapeutic applications.

Purpose of the Study:

  • To synthesize a novel molecular probe, 131I-FAPI, through radiosynthesis.
  • To evaluate the in vitro targeting capabilities and biological characteristics of the newly developed 131I-FAPI probe.
  • To assess the potential of 131I-FAPI as a diagnostic and therapeutic agent for FAP-expressing tumors.

Main Methods:

  • Radiosynthesis of 131I-FAPI using the chloramine-T method.
  • Assessment of radiolabeling yield and purity via thin-layer chromatography (TLC).
  • Evaluation of in vitro stability in PBS and serum, hydrophilicity via lipid-water partition coefficient, and cell uptake in PANC-1 and U87 cell lines.
  • Inhibition assays (CCK-8) and cell migration assays (scratch assay) to determine biological effects on U87 cells.

Main Results:

  • Successful radiosynthesis of 131I-FAPI with a radiolabeling rate of (84.9 ± 1.02)% and radiochemical purity over 80%.
  • The probe exhibited good in vitro stability and hydrophilic properties (lipid-water partition coefficient: -0.869 ± 0.025).
  • 131I-FAPI demonstrated specific binding to U87 cells, effectively inhibiting their proliferation and migration in vitro (P<0.001).

Conclusions:

  • The synthesized 131I-FAPI probe possesses favorable in vitro stability and hydrophilic characteristics.
  • 131I-FAPI exhibits specific binding to U87 glioma cells and effectively inhibits their proliferation and migration.
  • 131I-FAPI shows significant promise as a novel therapeutic probe for FAP-expressing cancers.

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