¹⁸F-labeled tracers targeting fibroblast activation protein

Area of Science:

• Oncology
• Radiochemistry
• Medical Imaging

Background:

• Cancer-associated fibroblasts (CAFs) overexpress fibroblast activation protein (FAP), a target for cancer theranostics.
• Gallium-68 tracers have limitations due to short half-life and batch size.
• Fluorine-18 labeling offers a longer-lived alternative for FAP-targeted imaging.

Purpose of the Study:

• To develop and evaluate novel fluorine-18 labeled fibroblast activation protein (FAP) imaging agents.
• To assess the in vitro and in vivo performance of these tracers for FAP-specific binding.
• To identify a suitable tracer for clinical positron emission tomography/computed tomography (PET/CT) imaging.

Main Methods:

• Radiolabeling of 6-fluoronicotinamide derivatives with fluorine-18 using aluminum fluoride complexes.
• In vitro binding assays using FAP-expressing HT-1080 cells and HEK-CD26 cells.
• Small animal PET imaging and biodistribution studies in HT-1080-FAP xenografted mice.
• Clinical PET/CT imaging in a patient with non-small cell lung cancer (NSCLC).

Main Results:

• ¹⁸F-labeled FAPI derivatives exhibited high affinity (EC₅₀ < 1 nm to 4.2 nm) and specific binding to FAP-expressing cells.
• [¹⁸F]AlF-FAPI-74 and -75 showed favorable renal excretion and high tumor-to-background ratios in small animal PET.
• ¹⁸F]AlF-FAPI-74 demonstrated excellent tumor uptake and rapid clearance in a patient with metastasized NSCLC.
• PET/CT imaging successfully visualized primary tumors and metastases.

Conclusions:

• [¹⁸F]AlF-labeled FAPI derivatives are effective positron emission tomography (PET) tracers.
• FAPI-74 exhibits promising performance for [¹⁸F]AlF-based FAP-imaging in clinical settings.
• This tracer enables visualization of FAP-positive tumors and metastases.