Synthesis and preliminary biological evaluation of a novel 99mTc-labeled small molecule for PD-L1 imaging

Abstract

In recent years, PD-1/PD-L1 checkpoint blockade immunotherapy with remarkable efficacy has set off a heat wave. The expression level of PD-L1, which plays a predictive role in anti-PD-1/PD-L1 therapy, could be quantified by noninvasive imaging with radiotracers. Herein, we introduced the synthesis and preliminary biological evaluation of a novel ^99mTc-labeled small molecule radiotracer [^99mTc]G₃C-CBM for PD-L1 imaging. [^99mTc]G₃C-CBM was achieved with high radiochemical purity (>96 %) and remained good stability in PBS and FBS. In competitive combination experiment, [^99mTc]G₃C-CBM was displaced by increasing concentrations of unlabeled G₃C-CBM, resulting in an IC₅₀ value of 41.25±2.23 nM for G₃C-CBM. The uptake of [^99mTc]G₃C-CBM in A375-hPD-L1 cells (17.51±2.08 %) was approximately 6.47 folds of that in A375 cells (2.71±0.36 %) after co-incubation for 2 h. The biodistribution results showed that the radioactivity uptake in A375-hPD-L1 tumor reached the maximum (0.35±0.01 %ID/g) at 2 h post injection, and the optimum tumor/muscle ratio of 2.94±0.29 occurred at the same time. In addition, [^99mTc]G₃C-CBM was quickly cleared from the blood with a clearance half-life of just 119.25 min. These results indicate that [^99mTc]G₃C-CBM is a potential SPECT PD-L1 imaging agent and is worthy of further study.

Keywords: (99m)Tc; PD-L1 imaging; Radiotracer; SPECT; Small molecule.