Open AccessPhotoacoustic imaging of elevated glutathione in models of lung cancer for companion diagnostic applications
Author(s) -
Melissa Y. Lucero,
Jefferson Chan
Publication year - 2021
Publication title -
nature chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.996
H-Index - 232
eISSN - 1755-4349
pISSN - 1755-4330
DOI - 10.1038/s41557-021-00804-0
Subject(s) - glutathione , lung cancer , chemistry , in vivo , photoacoustic imaging in biomedicine , cancer research , cancer , biomarker , molecular imaging , cancer cell , pathology , medicine , biochemistry , biology , enzyme , physics , microbiology and biotechnology , optics
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 N Ar 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.