A Novel Small Cyclic Peptide-Based 68Ga-Radiotracer for Positron Emission Tomography Imaging of PD-L1 Expression in Tumors

• DOI: 10.1021/acs.molpharmaceut.1c00694
• Publication Date: 2021-12-15T19:42:49Z
• Authors: Hanxiang Liu; Mei Hu; Jia Deng; Yan Zhao; Dengsai Peng; Yue Feng; Li Wang; Yue Chen; Lin Qiu
• Keywords: DOTA; Biodistribution

In the tumor microenvironment, programmed death protein 1 and ligand (PD-L1) signaling pathways help tumors escape immune system. We designed a gallium-68 (68Ga)-labeled small-molecule peptide-targeting PD-L1 used positron emission tomography/computed tomography (PET/CT) to detect dynamically monitor expression level of in tumors. S-Cyclo(ETSK)-SF-NH2 (SETSKSF) is cyclic peptide inhibitor comprising seven amino-acid residues. connected it with chelating agent DOTA, labeled DOTA-SETSKSF, short half-life nuclide Ga-68, measured stability 68Ga-2,2′,2″-(10-(2-((S)-1-((3S,6S,9S,18S)-18-((S)-1-((S)-1-amino-1-oxo-3-henylpropan-2-ylamino)-3-hydroxy-1-oxopropan-2-ylcarbamoyl)-6-((R)-1-hydroxyethyl)-3-(hydroxymethyl)-2,5,8,12-tetraoxo-1,4,7,13-tetraazacyclooctadecan-9-ylamino)-3-ydroxy-1-oxopropan-2-ylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (68Ga-DOTA-SETSKSF) normal saline (NS), phosphate-buffered (PBS), fetal bovine serum (FBS) vitro. conducted 68Ga-DOTA-SETSKSF affinity test, cell-specific uptake experiments, time-combined western blotting, laser confocal experiments confirm localization at cell determine uptake. Biodistribution imaging were performed using H1975, B16F10, A549 models. was successfully synthesized, radiochemical purity >99% after purification. The vitro >95% NS, PBS, FBS 37 °C 4 h incubation. Cell-binding confirmed that exhibited high H1975 low expression. clear (T1/2) from blood 14.48 ± 3.26 min. percentages injected dose per gram tissue (%ID/g) for 5.29 0.21 0.89 0.10 injection, respectively. tumor-to-muscle tumor-to-blood ratios 41.79 5.81 4.75 0.19 h, Apart tumor, kidney bladder showed accumulation because excreted through urinary PET/CT images tumors, which consistent results biodistribution experiments. convenient prepare, has stability, can be PD-L1, an extremely clinical application value.