Towards Personalized Medicine: Photoacoustic Imaging of Glutathione Enables Companion Diagnosis and Targeted Treatment of Lung Cancer

Abstract

<p>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.<br></p>

Acoustogenic Probes: A Demonstration to Introduce the Photoacoustic Effect via Analyte Sensing

“…Beyond the experiments we have performed in this demonstration, instructors are able (and encouraged) to vary the analyte being detected, as well as the readout of the setup to better teach the concepts of acoustogenic probes and photoacoustic imaging to their students, respectively. For instance, DER can be readily converted, in a single step using routine chemistry, to a large assortment of acoustogenic probes including examples for glutathione, 7 an important antioxidant, or copper, 2 an essential metal ion required by all living organisms (SI Figure S4). A student can be given a sample of an "unknown" analyte where they can be asked to use several target-responsive probes to determine its identity.…”