Photoacoustic imaging of elevated glutathione in models of lung cancer for companion diagnostic applications

Companion diagnostics (CDx) are powerful tests that can provide physicians with crucial biomarker information that can improve treatment outcomes by matching therapies to patients. Here, we report a photoacoustic imaging-based CDx (PACDx) for the selective detection of elevated glutathione (GSH) in a lung cancer model. GSH is abundant in most cells, so we adopted a physical organic chemistry approach to precisely tune the reactivity to distinguish between normal and pathological states. To evaluate the efficacy of PACDx in vivo, we designed a blind study where photoacoustic imaging was used to identify mice bearing lung xenografts. We also employed PACDx in orthotopic lung cancer and liver metastasis models to image GSH. In addition, we designed a matching prodrug, PARx, that uses the same SNAr chemistry to release a chemotherapeutic with an integrated PA readout. Studies demonstrate that PARx can inhibit tumour growth without off-target toxicity in a lung cancer xenograft model. Imaging-based companion diagnostics can provide real-time information to match therapies to patients; however, glutathione is abundant in most cells, making it an unlikely candidate for companion diagnosis. Now, a chemical probe has been developed that can detect elevated glutathione concentrations via photoacoustic imaging. Using this probe enables normal and pathological states in a lung cancer model to be distinguished.