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Article Abstract
Accurate identification of programmed cell death ligand 1 (PD-L1) expression is crucial for anti-tumor immunotherapy. However, the heterogeneity of PD-L1 expression in tumors makes it challenging to detect by immunohistochemistry. In this study, we developed two novel PD-L1 small-molecule PET tracers, [F]LGT-1 and [F]LGT-2, to enable the non-invasive and precise measurement of PD-L1 expression in tumors through PET imaging. The radiochemical yields for [F]LGT-1 and [F]LGT-2 were 12.54±2.73% and 10.54±2.21%, respectively, with both tracers exhibiting approximately 98% radiochemical purity and molar activities of 12.23±2.84 GBq/μmol and 11.41±1.47 GBq/μmol. Both tracers demonstrated good stability in PBS (pH 7.4) and mouse serum after 2 hours of incubation. In cellular uptake assays, [F]LGT-1 achieved a maximum uptake of 5.47±0.03 %AD at 4 hours, which could be significantly inhibited by the non-radioactive compound LGT-1. In contrast, [F]LGT-2 exhibited high non-specific uptake in tumor cells. PET imaging revealed that [F]LGT-1 quickly accumulated in tumors within 5 minutes, achieving an uptake of 1.48±0.15 %ID/mL, and maintained a stable level for 60 minutes, while [F]LGT-2 showed minimal tumor uptake. Additionally, [F]LGT-1 had significantly lower liver uptake compared to [F]LGT-2. Despite the high uptake in non-target tissues for [F]LGT-1, which complicates its application, this study provides new insights for developing novel PD-L1 small-molecule tracers, with further optimization of the tracers currently in progress.
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| http://dx.doi.org/10.1016/j.bmcl.2025.130187 | DOI Listing |
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