A novel peptide-based probe^(99m)Tc-PEG_(6)-RD-PDP2 for the molecular imaging of tumor PD-L2 expression

摘要

Tumor-related PD-L2 expression is associated with the clinical efficacy of PD-1/PD-L1 blockade therapy.PD-L2-specific imaging can help selecting patients for appropriate immunotherapy.In this study,a PD-L2-targeting peptide(PDP2)was screened by the one-bead one-compound combinatorial library approach.Using the retro-inverso D-peptide of PDP2(RD-PDP2)and PEGylation strategies,we developed a novel Tc-99m-labeled PD-L2-targeting peptide as a SPECT tracer(^(99m)Tc-PEG_(6)-RD-PDP2)for imaging of tumor PD-L2 expression.The radiolabeling yield of ^(99m)Tc-PEG_(6)-RD-PDP2 was greater than 95%by the standard HYNIC/tricine/TPPTS labeling procedure.^(99m)Tc-PEG_(6)-RD-PDP2 displayed high PD-L2-binding specificity both in vitro and in vivo.SPECT/CT imaging with^(99m)Tc-PEG_(6)-RD-PDP2 showed that the A549-PD-L2tumors were clearly visualized,whereas the signals in PD-L2-negative A549 tumors were much lower.In vivo blocking study suggested that the tumor uptake of^(99m)Tc-PEG_(6)-RD-PDP2 was PD-L2 specifically mediated.^(99m)Tc-PEG_(6)-RD-PDP2 is a promising SPECT probe for the non-invasive imaging of tumor PD-L2expression and has a great potential in guiding the anti-PD-1 or anti-PD-L1 immunotherapy of cancer.