Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

Small molecules offer some advantages for developing PET tracers and are therefore a promising approach for imaging and therapy monitoring of PD-L1 positive tumors. Here, we report six biphenyl PD-L1 radioligands, using the NODA-GA-chelator for efficient copper-64 complexation. These radioligands contain varying numbers of sulfonic and/or phosphon-ic acid groups, serving as hydrophilizing units to lower the log D7.4 value down to –4.28. Binding affinities of compounds were evaluated using saturation binding and a real-time binding assay, with lowest binding affinity of 21 nM. Small ani-mal PET imaging revealed vastly different pharmacokinetic profiles, depending on the quantity and type of hydrophiliz-ing units. Of the investigated radioligands, [64Cu]Cu-3 showed the most favorable kinetics in vitro. This was also found in vivo, with a predominantly renal clearance and a specific uptake in the PD-L1-positive tumor. With further modifications, this compound could be a promising candidate for imaging of PD-L1 in the clinical setting.