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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

DOI: 10.1021/acs.inorgchem.9b01132 DOI Help

Authors: Veronica Clavijo Jordan (University of Texas; Harvard Medical School) , Alia Al-ebraheem (McMaster University) , Kalotina Geraki (Diamond Light Source) , Eric Dao (McMaster University) , Andre F. Martins (University of Texas Southwestern Medical Center; University of Texas at Dallas; Eberhard Karls University Tuebingen) , Sara Chirayil (University of Texas Southwestern Medical Center) , Michael Farquharson (McMaster University) , A. Dean Sherry (University of Texas Southwestern Medical Center; University of Texas at Dallas)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Inorganic Chemistry

State: Published (Approved)
Published: July 2019
Diamond Proposal Number(s): 14747

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.

Subject Areas: Chemistry, Biology and Bio-materials, Medicine

Instruments: I18-Microfocus Spectroscopy