Preclinical characterization of a novel FAP-targeted PET tracer, [⁶⁸Ga]Ga-CB6NT-FAPI

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Fibroblast Activation Protein (FAP) is a key target in tumor stroma for molecular imaging.
• Existing FAP-targeted tracers have varying pharmacokinetic profiles.

Purpose of the Study:

• To develop and evaluate a novel FAP-targeted positron emission tomography (PET) tracer, [68Ga]Ga-CB6NT-FAPI.
• To assess its radiolabeling efficiency, stability, specificity, and in vivo performance.

Main Methods:

• Radiolabeling of [68Ga]Ga-CB6NT-FAPI under mild conditions.
• In vitro cell uptake studies with FAP-positive and FAP-negative cells.
• In vivo PET/MR imaging and biodistribution studies in a U87MG xenograft model.
• Blocking studies to confirm target specificity.

Main Results:

• High radiochemical purity (>99.9%) and excellent in vitro stability were achieved.
• Specific binding to FAP-positive cells was confirmed, with significantly higher uptake compared to FAP-negative cells.
• In vivo imaging demonstrated clear tumor uptake and favorable contrast, with specific accumulation confirmed by blocking studies.
• The tracer showed renal clearance with partial hepatobiliary involvement.

Conclusions:

• [68Ga]Ga-CB6NT-FAPI is a highly efficient and stable FAP-targeted PET tracer.
• It demonstrates excellent specificity and tumor targeting capabilities in preclinical models.
• CB6NT-FAPI offers a differentiated pharmacokinetic profile, expanding options for FAP-targeted PET imaging.