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

M. Veronica Clavijo Jordan, Su Tang Lo, Shiuhwei Chen, Christian Preihs, Sara Chirayil, Shanrong Zhang, Payal Kapur, Wen Hong Li, Luis M. De Leon-Rodriguez, Angelo J M Lubag, Neil M. Rofsky, A. Dean Sherry

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)E5464-E5471
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number37
DOIs
StatePublished - Sep 13 2016

Keywords

  • Cancer
  • Glucose
  • MRI
  • Prostate
  • Zinc

ASJC Scopus subject areas

  • General

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