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Inorg Chem. 2019 Jul 1. doi: 10.1021/acs.inorgchem.9b01132. [Epub ahead of print]

Synchrotron Radiation X-ray Fluorescence Elemental Mapping in Healthy versus Malignant Prostate Tissues Provides New Insights into the Glucose-Stimulated Zinc Trafficking in the Prostate As Discovered by MRI.

Author information

1
Advanced Imaging Research Center and Department of Radiology , University of Texas Southwestern Medical Center , Dallas , Texas 75390 , United States.
2
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital , Harvard Medical School , Charlestown , Massachusetts 02129 , United States.
3
School of Interdisciplinary Science , McMaster University , Hamilton , Ontario L8S 4K1 , Canada.
4
Diamond Light Source , Harwell, Didcot OX11 0DE , United Kingdom.
5
Department of Physics and Astronomy , McMaster University , Hamilton , Ontario L8S 4K1 , Canada.
6
Department of Chemistry , University of Texas at Dallas , Richardson , Texas 75080 , United States.
7
Werner Siemens Imaging Center , Eberhard Karls University Tuebingen , Tuebingen , 72076 , Germany.
8
Vitalquan, LLC , Dallas , Texas 75235 , United States.

Abstract

Prostatic zinc content is a known biomarker for discriminating normal healthy tissue from benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Given that zinc content is not readily measured without a tissue biopsy, we have been exploring noninvasive imaging methods to detect these diagnostic differences using a zinc-responsive MRI contrast agent. During imaging studies in mice, we observed that a bolus of glucose stimulates secretion of zinc from the prostate of fasted mice. This discovery allowed the use of a Gd-based zinc sensor to detect differential zinc secretion in regions of healthy versus malignant prostate tissue in a transgenic adenocarcinoma mouse model of PCa. Here, we used a zinc-responsive MRI agent to detect zinc release across the prostate during development of malignancy and confirm the loss of total tissue zinc by synchrotron radiation X-ray fluorescence (μSR-XRF). Quantitative μSR-XRF results show that the lateral lobe of the mouse prostate uniquely accumulates high concentrations of zinc, 1.06 ± 0.08 mM, and that the known loss of zinc content in the prostate is only observed in the lateral lobe during development of PCa. Additionally, we confirm that lesions identified by a loss of zinc secretion indeed represent malignant neoplasia and that the relative zinc concentration in the lesion is reduced to 0.370 ± 0.001 mM. The μSR-XRF data also provided insights into the mechanism of zinc secretion by showing that glucose promotes movement of zinc pools (∼1 mM) from the glandular lumen of the lateral lobe of the mouse prostate into the stromal/smooth muscle surrounding the glands. Co-localization of zinc and gadolinium in the stromal/smooth muscle areas as detected by μSR-XRF confirm that glucose initiates secretion of zinc from intracellular compartments into the extracellular spaces of the gland where it binds to the Gd-based agent and albumin promoting MR image enhancement.

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