Pharmaceutical Research, 2017, Vol.34(12), pp.2698-2709
To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11095-017-2200-9 Byline: Jace W. Jones (1), Isabel L. Jackson (2), Zeljko Vujaskovic (2), Michael D. Kaytor (3), Maureen A. Kane (1) Keywords: biomarkers; genistein; lung injury; metabolomics; radiation Abstract: Purpose Biomarkers serve a number of purposes during drug development including defining the natural history of injury/disease, serving as a secondary endpoint or trigger for intervention, and/or aiding in the selection of an effective dose in humans. BIO 300 is a patent-protected pharmaceutical formulation of nanoparticles of synthetic genistein being developed by Humanetics Corporation. The primary goal of this metabolomic discovery experiment was to identify biomarkers that correlate with radiation-induced lung injury and BIO 300 efficacy for mitigating tissue damage based upon the primary endpoint of survival. Methods High-throughput targeted metabolomics of lung tissue from male C57L/J mice exposed to 12.5 Gy whole thorax lung irradiation, treated daily with 400 mg/kg BIO 300 for either 2 weeks or 6 weeks starting 24 h post radiation exposure, were assayed at 180 d post-radiation to identify potential biomarkers. Results A panel of lung metabolites that are responsive to radiation and able to distinguish an efficacious treatment schedule of BIO 300 from a non-efficacious treatment schedule in terms of 180 d survival were identified. Conclusions These metabolites represent potential biomarkers that could be further validated for use in drug development of BIO 300 and in the translation of dose from animal to human. Author Affiliation: (1) School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland, 20 N. Pine Street, Baltimore, Maryland, 21201, USA (2) School of Medicine, Division of Translational Radiation Sciences Department of Radiation Oncology, University of Maryland, Baltimore, 21201, Maryland, USA (3) Humanetics Corporation, Edina, 55435, Minnesota, USA Article History: Registration Date: 30/05/2017 Received Date: 17/03/2017 Accepted Date: 30/05/2017 Online Date: 02/10/2017 Article note: Electronic supplementary material The online version of this article (doi: 10.1007/s11095-017-2200-9) contains supplementary material, which is available to authorized users.
biomarkers ; genistein ; lung injury ; metabolomics ; radiation
View full text in Springer (Subscribers only)