Companion diagnostics (CDx) represent a new frontier in personalized medicine that promises to improve treatment outcomes by matching therapies to patients. Currently, these tests are limited in scope and cannot report on real-time changes associated with disease progression and remediation. To address this, we have developed the first photoacoustic imaging-based CDx (PACDx) for the selective detection of elevated glutathione (GSH) in lung cancer. Since GSH is abundant in most cells, it was essential to tune the reactivity of the benzenesulfonyl-based trigger to distinguish between normal and pathological states. Moreover, we designed a matching prodrug, PARx, that utilizes the same mechanism to release both a chemotherapeutic (Gemcitabine) and a PA readout. We demonstrate that PARx can inhibit tumor growth while sparing all other tissue from off target toxicity in a A549 lung cancer xenograft model. We envision that this work will establish a new standard for personalized medicine by employing a unique imaging-based approach.
PACDx ChemRxiv SI Final