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

preprint
revised on 27.04.2020, 22:20 and posted on 28.04.2020, 12:39 by Melissa Lucero, Jefferson Chan

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.

Funding

Chemical Tools to Study the Role of Biological Aldehydes

National Institute of General Medical Sciences

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History

Email Address of Submitting Author

jeffchan@illinois.edu

Institution

University of Illinois at Urbana-Champaign

Country

United States

ORCID For Submitting Author

0000-0003-4139-4379

Declaration of Conflict of Interest

No conflict of interest

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