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

ABSTRACT: 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 S_NAr 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.

SUBMITTER: Lucero MY

PROVIDER: S-EPMC8629919 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Lucero Melissa Y MY Chan Jefferson J

Nature chemistry 20211025 12

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 evalu ...[more]

PMID: 34697400

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Dataset Information

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

Publications

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

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