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Angew Chem Int Ed Engl. 2019 Oct 21;58(43):15512-15517. doi: 10.1002/anie.201909429. Epub 2019 Sep 17.

Development of Zinc-Specific iCEST MRI as an Imaging Biomarker for Prostate Cancer.

Yuan Y1,2, Wei Z1, Chu C1,2, Zhang J1, Song X1,2, Walczak P1,2, Bulte JWM1,2,3.

Author information

1
The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
Department of Oncology, Department of Biomedical Engineering, Department of Chemical Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

The healthy prostate contains the highest concentration of mobile zinc in the body. As this level decreases dramatically during the initial development of prostate cancer, in vivo detection of prostate zinc content may be applied for diagnosis of prostate cancer. Using 19 F ion chemical exchange saturation transfer magnetic resonance imaging (iCEST MRI) and TF-BAPTA as a fluorinated Zn-binding probe with micromolar sensitivity, we show that iCEST MRI is able to differentiate between normal and malignant prostate cells with a 10-fold difference in contrast following glucose-stimulated zinc secretion in vitro. The iCEST signal decreased in normal prostate cells upon downregulation of the ZIP1 zinc transporter. In vivo, using an orthotopic prostate cancer mouse model and a transgenic adenocarcinoma of the mouse prostate (TRAMP) model, a gradual decrease of >300 % in iCEST contrast following the transition of normal prostate epithelial cells to cancer cells was detected.

KEYWORDS:

MRI; imaging agents; prostate cancer; zinc

PMID:
31430007
DOI:
10.1002/anie.201909429

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