Author:
Clavijo Jordan M. Veronica,Lo Su-Tang,Chen Shiuhwei,Preihs Christian,Chirayil Sara,Zhang Shanrong,Kapur Payal,Li Wen-Hong,De Leon-Rodriguez Luis M.,Lubag Angelo J. M.,Rofsky Neil M.,Sherry A. Dean
Abstract
Many secretory tissues release Zn(II) ions along with other molecules in response to external stimuli. Here we demonstrate that secretion of Zn(II) ions from normal, healthy prostate tissue is stimulated by glucose in fasted mice and that release of Zn(II) can be monitored by MRI. An ∼50% increase in water proton signal enhancement is observed in T1-weighted images of the healthy mouse prostate after infusion of a Gd-based Zn(II) sensor and an i.p. bolus of glucose. Release of Zn(II) from intracellular stores was validated in human epithelial prostate cells in vitro and in surgically exposed prostate tissue in vivo using a Zn(II)-sensitive fluorescent probe known to bind to the extracellular surface of cells. Given the known differences in intracellular Zn(II) stores in healthy versus malignant prostate tissues, the Zn(II) sensor was then evaluated in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model in vivo. The agent proved successful in detecting small malignant lesions as early as 11 wk of age, making this noninvasive MR imaging method potentially useful for identifying prostate cancer in situations where it may be difficult to detect using current multiparametric MRI protocols.
Funder
Office of Extramural Research, National Institutes of Health
HHS | NIH | National Cancer Institute
The American Diabetes Association Research Foundation
Robert A. Welch Foundation
Publisher
Proceedings of the National Academy of Sciences
Cited by
83 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献