Development of a Dual-Factor Activatable Covalent Targeted Photoacoustic Imaging Probe for Tumor Imaging.

Autor: Song J; Department of Pharmacology and Chemical Biology, Emory University, Atlanta, Georgia, 30322, United States., Zhai T; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA., Hahm HS; Department of Pharmacology and Chemical Biology, Emory University, Atlanta, Georgia, 30322, United States., Li Y; Department of Radiology and Imaging Science, Emory University, Atlanta, Georgia, 30322, United States., Mao H; Department of Radiology and Imaging Science, Emory University, Atlanta, Georgia, 30322, United States., Wang X; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA., Jo J; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA., Chang JW; Department of Pharmacology and Chemical Biology, Emory University, Atlanta, Georgia, 30322, United States.; Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia, 30322, United States.; Winship Cancer Institute, Emory University, Atlanta, Georgia, 30322, United States.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Oct 01; Vol. 63 (40), pp. e202410645. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1002/anie.202410645
Abstrakt: Photoacoustic imaging (PAI) is an emerging modality in biomedical imaging with superior imaging depth and specificity. However, PAI still has significant limitations, such as the background noise from endogenous chromophores. To overcome these limitations, we developed a covalent activity-based PAI probe, NOx-JS013, targeting NCEH1. NCEH1, a highly expressed and activated serine hydrolase in aggressive cancers, has the potential to be employed for the diagnosis of cancers. We show that NOx-JS013 labels active NCEH1 in live cells with high selectivity relative to other serine hydrolases. NOx-JS013 also presents its efficacy as a hypoxia-responsive imaging probe in live cells. Finally, NOx-JS013 successfully visualizes aggressive prostate cancer tumors in mouse models of PC3, while being negligibly detected in tumors of non-aggressive LNCaP mouse models. These findings show that NOx-JS013 has the potential to be used to develop precision PAI reagents for detecting metastatic progression in various cancers.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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