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

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 ID-peptide of PDP2 (RD-PDP2) and PEGylation strategies, we developed a novel Tc-99m-labeled PD-L2-targeting peptide as a SPECT tracer (Tc-99(m)-PEG(6)-RD-PDP2) for imaging of tumor PD-L2 expression. The radiolabeling yield of Tc-99m-PEG(6)-RD-PDP2 was greater than 95% by the standard HYNIC/tricine/TPPTS labeling procedure. Tc-99m-PEG(6)-RD-PDP2 displayed high PD-L2-binding specificity both in vitro and in vivo. SPECT/CT imaging with Tc-99(m)-PEG(6)-RD-PDP2 showed that the A549-PD-L2 tumors 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 Tc-99m-PEG(6)-RD-PDP2 was PD-L2 specifically mediated. Tc-99m-PEG(6)-RD-PDP2 is a promising SPECT probe for the non-invasive imaging of tumor PD-L2 expression and has a great potential in guiding the anti-PD-1 or anti-PD-L1 immunotherapy of cancer. (C) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.