A rationally designed nuclei-targeting FAPI 04-based molecular probe with enhanced tumor uptake for PET/CT and...

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Radiochemistry

Background:

• Fibroblast activation protein inhibitor (FAPI)-based probes are used in PET/CT for tumor diagnosis.
• Current FAPI probes have limitations including rapid clearance and potential false negatives.
• FAPI has been underexplored in optical imaging, necessitating probe modification.

Purpose of the Study:

• To develop a modified FAPI-based probe with enhanced properties for both PET/CT and fluorescence imaging.
• To introduce methylene blue (MB) to FAPI probes to impart nuclei-targeting and fluorescence capabilities.
• To evaluate the added value of FAPI-based fluorescence imaging alongside PET/CT and explore intraoperative applications.

Main Methods:

• Designed and synthesized NOTA-FAPI-MB, a novel probe conjugating MB to FAPI for dual-mode imaging.
• Evaluated probe targeting efficacy in FAP-transfected cells and cancer-associated fibroblasts (CAFs).
• Conducted in vivo PET/CT and fluorescence imaging in tumor-bearing mice and assessed human HCC tissues.

Main Results:

• NOTA-FAPI-MB exhibited superior targeting of FAP-expressing cells due to MB's affinity for nucleic acids.
• PET/CT imaging showed higher tumor uptake for [18F]F-NOTA-FAPI-MB compared to [18F]F-FDG.
• In vivo fluorescence imaging demonstrated prolonged tumor retention (24h) and superior lesion/margin delineation versus ICG.

Conclusions:

• NOTA-FAPI-MB, combining FAPI and MB, demonstrated enhanced targeting and retention via nuclear delivery.
• The probe showed favorable PET/CT performance and significant advantages in fluorescence imaging for tumor detection.
• Results suggest NOTA-FAPI-MB's potential as an adjunct to PET/CT and for intraoperative surgical guidance.