Preclinical evaluation of [68Ga]Ga-MRCP: a potential radiotracer for imaging PD-L1 expression in colorectal cancer.

The approval of immune checkpoint inhibitors has made significant progress in the clinical treatment of colorectal cancer. In clinical practice, it is crucial to identify patients who can potentially benefit from immunotherapy and to accurately evaluate their treatment responses. Herein, we developed a cyclic peptide-based PET tracer, [68Ga]Ga-MRCP, which can noninvasively and specifically detect tumor PD-L1 expression in vivo and serve as a tool for evaluating immunotherapy efficacy. A mild radiolabeling method afforded the tracer [68Ga]Ga-MRCP with high radiochemical yield (RCY) and radiochemical purity (RCP), along with excellent stability. Binding affinity assays demonstrated that the tracer exhibits moderate affinity for PD-L1 (KD = 43.58 ± 6.48 nM). In vitro cellular uptake experiments revealed that the tracer uptake in PD-L1 high-expression RKO cells (1.92 ± 0.12 %AD) was significantly higher than that in PD-L1 low-expression SW480 cells (0.61 ± 0.08 %AD). PET imaging further substantiated that the tracer uptake in RKO tumors (3.23 ± 0.06 %ID/mL) was markedly higher than that in SW480 tumors (2.05 ± 0.07 %ID/mL). Notably, the tracer showed potential in quantifying dynamic changes in PD-L1 expression during immunotherapy. Collectively, this study confirms that [68Ga]Ga-MRCP can specifically target PD-L1, highlighting its potential for dynamically monitoring PD-L1 expression during immunotherapy.