Antibody pretargeting: A flexible tool for in-vivo imaging with application to imaging of Brown Adipose Tissue

Brown adipose tissue (BAT), recently identified in adult humans, plays an important role in thermoregulation and metabolism. Accurate in-vivo quantification of BAT is essential for studying metabolic dysfunction, yet current imaging methods remain limited in sensitivity and specificity.¹

This project aims to develop a selective PET imaging strategy based on an anti-BAT antibody conjugated with an ¹⁸F-labeled probe. Phosphonium trifluoroborate was chosen as the ¹⁸F scaffold because of its high stability and efficient radiolabeling by isotope exchange.²

To maximize in vivo labeling, a pretargeting approach will be employed³: an anti-BAT antibody functionalized with trans-cyclooctene will first bind its target, followed by rapid reaction with an ¹⁸F-phosphonium trifluoroborate-tetrazine probe through bioorthogonal click chemistry. Optimized syntheses of phosphonium trifluoroborates and tetrazines, including a telescoped strategy, enabled gram-scale preparation of a library of probes. These compounds will be evaluated to identify candidates with optimal selectivity, sensitivity, and imaging contrast for BAT detection.