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Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5464-71. doi: 10.1073/pnas.1609450113. Epub 2016 Aug 25.

Zinc-sensitive MRI contrast agent detects differential release of Zn(II) ions from the healthy vs. malignant mouse prostate.

Author information

1
Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8568; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8896;
2
Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9039; Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9039;
3
Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8568;
4
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9039; Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9110;
5
Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8568; School of Chemical Sciences, The University of Auckland, Auckland 1142, New Zealand;
6
Medichlorian Dynamics, LLC, Plano, TX 75244;
7
Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8568; Department of Radiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8896; Department of Chemistry, University of Texas at Dallas, Richardson, TX 75083 dean.sherry@utsouthwestern.edu.

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.

KEYWORDS:

MRI; cancer; glucose; prostate; zinc

PMID:
27562169
PMCID:
PMC5027418
DOI:
10.1073/pnas.1609450113
[Indexed for MEDLINE]
Free PMC Article

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