title: Zinc-sensitive MRI contrast agent detects differential release of Zn(II) ions from the healthy vs. malignant mouse prostate.
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.
authors: 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;
authors: M Veronica
authors: MV
authors: Clavijo Jordan
authors: 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;
authors: Su-Tang
authors: ST
authors: Lo
authors: 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;
authors: Shiuhwei
authors: S
authors: Chen
authors: Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8568;
authors: Christian
authors: C
authors: Preihs
authors: Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8568;
authors: Sara
authors: S
authors: Chirayil
authors: Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390-8568;
authors: Shanrong
authors: S
authors: Zhang
authors: 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;
authors: Payal
authors: P
authors: Kapur
authors: 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;
authors: Wen-Hong
authors: WH
authors: Li
authors: 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;
authors: Luis M
authors: LM
authors: De Leon-Rodriguez
authors: Medichlorian Dynamics, LLC, Plano, TX 75244;
authors: Angelo J M
authors: AJ
authors: Lubag
authors: 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;
authors: Neil M
authors: NM
authors: Rofsky
authors: 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.
authors: A Dean
authors: AD
authors: Sherry
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D011467:Prostate / Q000000981:diagnostic imaging / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D015032:Zinc
keywords: MRI; cancer; glucose; prostate; zinc