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

Melissa Y. Lucero, Jefferson Chan

Research output: Contribution to journalArticlepeer-review

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 SNAr 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.
Original languageEnglish (US)
Pages (from-to)1248-1256
Number of pages9
JournalNature Chemistry
Volume13
Issue number12
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • General Chemical Engineering
  • General Chemistry

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