A Radiofluorinated Nanobody PET Tracer to Dynamically Visualize Differential Nectin4 Expression In Vivo

Area of Science:

• Biomedical imaging
• Molecular imaging
• Radiochemistry

Background:

• Nectin4 is a promising therapeutic target for several cancer types.
• Developing diagnostic tools for Nectin4 is crucial for targeted therapies.

Purpose of the Study:

• To develop and evaluate a novel nanobody-based PET tracer for Nectin4.
• To assess the diagnostic potential of the tracer in preclinical cancer models.

Main Methods:

• Selection and preparation of a nanobody-based PET tracer using [18F]AlF radiolabeling.
• In vitro and in vivo evaluation of tracer affinity, specificity, and tumor uptake in cell lines and animal models.
• Dynamic PET imaging and kinetic analysis to characterize pharmacokinetic behavior and Nectin4 expression correlation.

Main Results:

• The [18F]AlF-labeled nanobody tracer demonstrated high affinity for Nectin4 (KD = 6.77 nM).
• The tracer successfully visualized Nectin4-expressing lesions in vivo.
• PET signal intensity correlated with histological Nectin4 expression levels in tumor models.

Conclusions:

• The developed nanobody-based PET tracer is a specific and effective tool for visualizing Nectin4 expression.
• This tracer holds potential for clinical application in diagnosing and monitoring Nectin4-positive cancers.