@article{f9619fbfd4f84b38aba6cdeb9f615318,
title = "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 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.",
author = "Lucero, {Melissa Y.} and Jefferson Chan",
note = "Funding Information: This work was supported by the National Institutes of Health (R35GM133581). M.Y.L acknowledges the Alfred P. Sloan Foundation for financial support. Major funding for the 500-MHz Bruker CryoProbeTM was provided by the Roy J. Carver Charitable Trust (Muscatine, Iowa; grant no. 15-4521) to the School of Chemical Sciences NMR Lab. The Q-TOF Ultima mass spectrometer was purchased in part with a grant from the National Science Foundation, Division of Biological Infrastructure (DBI-0100085). We also acknowledge the Core Facilities at the Carl R. Woese Institute for Genomic Biology for access to the Zeiss LSM 700 confocal microscope and corresponding software. We also acknowledge I. Dobrucka and the Molecular Imaging Laboratory at the Beckman Institute for use of the IVIS imaging system. M.Y.L. thanks H. Knox for initial animal training and assistance with the NanoZoomer. We thank T. Bearrood and C. Anorma for assistance with initial confocal imaging experiments, L. Akin for aid with mass spectrometry experiments, S. Anakk and A. Dean for help with interpreting results from H&E staining experiments, N. Herndon and J. Xu for help with generating the orthotopic lung cancer and liver metastasis models, S. Gardner for providing 4T1 tumour models, J. Sarol and A. Kaur from Biostatistics, Epidemiology, & Research Design at the Interdisciplinary Health Sciences Institute (UIUC) for aid in statistical analysis, and A. Bennet for helpful discussions. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2021",
month = dec,
doi = "10.1038/s41557-021-00804-0",
language = "English (US)",
volume = "13",
pages = "1248--1256",
journal = "Nature Chemistry",
issn = "1755-4349",
publisher = "Nature Publishing Group",
number = "12",
}