%0 Journal Article
%A Krutzek, Fabian
%A Donat, Cornelius K
%A Ullrich, Martin
%A Zarschler, Kristof
%A Ludik, Marie-Charlotte
%A Feldmann, Anja
%A Loureiro, Liliana R
%A Kopka, Klaus
%A Stadlbauer, Sven
%T Design and Biological Evaluation of Small-Molecule PET-Tracers for Imaging of Programmed Death Ligand 1.
%J Cancers
%V 15
%N 9
%@ 2072-6694
%C Basel
%I MDPI
%M DKFZ-2023-00977
%P 2638
%D 2023
%X Noninvasive molecular imaging of the PD-1/PD-L1 immune checkpoint is of high clinical relevance for patient stratification and therapy monitoring in cancer patients. Here we report nine small-molecule PD-L1 radiotracers with solubilizing sulfonic acids and a linker-chelator system, designed by molecular docking experiments and synthesized according to a new, convergent synthetic strategy. Binding affinities were determined both in cellular saturation and real-time binding assay (LigandTracer), revealing dissociation constants in the single digit nanomolar range. Incubation in human serum and liver microsomes proved in vitro stability of these compounds. Small animal PET/CT imaging, in mice bearing PD-L1 overexpressing and PD-L1 negative tumors, showed moderate to low uptake. All compounds were cleared primarily through the hepatobiliary excretion route and showed a long circulation time. The latter was attributed to strong blood albumin binding effects, discovered during our binding experiments. Taken together, these compounds are a promising starting point for further development of a new class of PD-L1 targeting radiotracers.
%K PD-L1 (Other)
%K PET imaging (Other)
%K immune checkpoint inhibitors (Other)
%K organic synthesis (Other)
%K radiotracer (Other)
%K small molecules (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:37174103
%2 pmc:PMC10177516
%R 10.3390/cancers15092638
%U https://inrepo02.dkfz.de/record/276071