Towards Personalized Medicine: Photoacoustic Imaging of Glutathione Enables Companion Diagnosis and Targeted Treatment of Lung Cancer
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
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, we utilized a physical organic approach to precisely tune the chemical reactivity to distinguish between normal and pathological states. In blinded studies, PACDx was applied to identify mice bearing lung tumors. Moreover, we designed a matching prodrug, PARx, that utilizes the same mechanism to release a chemotherapeutic with a PA readout. We demonstrate that PARx can inhibit tumor growth without off-target toxicity in a lung cancer xenograft model. We envision that this work will establish a new standard for personalized medicine by employing a unique imaging-based approach.
Chemical Tools to Study the Role of Biological Aldehydes
National Institute of General Medical SciencesFind out more...