Design, Synthesis, and Biological Evaluation of Small-Molecule-Based Radioligands with Improved Pharmacokinetic Properties for Imaging of Programmed Death Ligand 1.

ABSTRACT: Small molecules offer some advantages for developing positron emission tomography (PET) tracers and are therefore a promising approach for imaging and therapy monitoring of programmed death ligand 1 (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 phosphonic acid groups, serving as hydrophilizing units to lower the log D_7.4 value down to -4.28. The binding affinities of compounds were evaluated using saturation binding and a real-time binding assay, with a highest binding affinity of 21 nM. Small-animal PET imaging revealed vastly different pharmacokinetic profiles depending on the quantity and type of hydrophilizing units.

SUBMITTER: Krutzek F 

PROVIDER: S-EPMC10726354 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature