Radiolabelled FGF-2 for Imaging Activated Fibroblasts in the Tumor Micro-Environment

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Tumor-associated fibroblasts (TAFs) promote cancer progression and metastasis.
• Fibroblast growth factor receptors (FGFRs), particularly FGFR-2c, are overexpressed in TAFs and linked to advanced cancer stages.
• A non-invasive method to visualize FGFR-2c expression in vivo is needed for better cancer detection and management.

Purpose of the Study:

• To develop and evaluate a novel radiopharmaceutical, 99mTc-labeled fibroblast growth factor-2 (99mTc-FGF-2), for non-invasive imaging of FGFR-2c expression in metastatic cancer.
• To assess the in vitro binding affinity and in vivo tumor targeting of 99mTc-FGF-2.

Main Methods:

• Fibroblast growth factor-2 (FGF-2) was labeled with Technetium-99m (99mTc).
• The radiolabeling efficiency and specific activity were determined.
• In vitro binding assays were performed using human keratinocytes.
• In vivo studies were conducted in mice bearing sarcoma allografts, with imaging using a high-resolution gamma camera.

Main Results:

• 99mTc-FGF-2 was successfully synthesized with high specific activity, requiring purification.
• In vitro studies demonstrated nanomolar binding affinity (Kd = 3.36 × 10^-9 M) to cells expressing FGFR-2c.
• In vivo, 99mTc-FGF-2 exhibited rapid and high tumor uptake in mice, achieving a high Tumor/Blood ratio at 24 hours post-injection (26.1 %ID/g and 12.9 %ID) with acceptable biodistribution.

Conclusions:

• 99mTc-FGF-2 is a promising new radiopharmaceutical for imaging FGFR-2c.
• The agent demonstrates effective tumor targeting and accumulation in vivo.
• This tool has the potential for non-invasive imaging of TAFs in human metastatic cancers.