Photoacoustic imaging of elevated glutathione in models of lung cancer for companion diagnostic applications.
Nat Chem
; 13(12): 1248-1256, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34697400
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Biomarcadores de Tumor
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Arilsulfonatos
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Colorantes
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Glutatión
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Indoles
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Neoplasias Pulmonares
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
Idioma:
En
Revista:
Nat Chem
Asunto de la revista:
QUIMICA
Año:
2021
Tipo del documento:
Article