ICOS-Targeted Peptide Imaging Informs Therapeutic Response of STING Agonist in Lung Adenocarcinoma

The innovation of cancer immunotherapy is improving clinical theranostics for lung cancer. Given the variation of therapeutic effects among patients, there is an urgent need to develop novel tools for precisely evaluating immune responses. Methods: Herein, we first described the potential of the inducible costimulator (ICOS) as a promising imaging biomarker for assessing cancer immunotherapy through multiple omics datasets and subsequently developed ⁶⁸Ga-DOTA-ICOSpep, a novel peptide-based PET tracer targeting human ICOS. We characterized ICOS expression patterns via flow cytometry and immunofluorescence and performed ⁶⁸Ga-DOTA-ICOSpep PET imaging and cytokine testing on humanized A549 cell line-derived mouse models receiving cyclic guanosine monophosphate-adenosine monophosphate and diABZI stimulator of interferon genes (STING) agonist treatment. Results: ⁶⁸Ga-DOTA-ICOSpep could capture human ICOS-positive activated T cells with high specificity in vivo, which was validated via linear regression analysis between tumor PET region-of-interest quantifications against ICOS immunohistochemistry staining as well as a CD3 depletion study. Conclusion: ICOS PET imaging enabled precise evaluation of therapeutic responses and increased proinflammatory cytokine release induced by the STING agonist. Our data demonstrated that ICOS is a robust biomarker for assessing immune responses, and ⁶⁸Ga-DOTA-ICOSpep PET imaging is a reliable tool for predicting and monitoring therapeutic effects of cancer immunotherapy in lung adenocarcinoma.