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

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 19F ion chemical exchange satu...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-10, Vol.58 (43), p.15512-15517
Main Authors: Yuan, Yue, Wei, Zhiliang, Chu, Chengyan, Zhang, Jia, Song, Xiaolei, Walczak, Piotr, Bulte, Jeff W. M.
Format: Article
Language:English
Subjects:
Adenocarcinoma
Animals
Biomarkers
Biomarkers, Tumor - metabolism
Cell Line, Tumor
Contrast Media - chemistry
Disease Models, Animal
Egtazic Acid - analogs & derivatives
Egtazic Acid - chemistry
Epithelial cells
Fluorination
Fluorine - chemistry
Humans
imaging agents
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Male
Medical imaging
Mice
Mice, Transgenic
MRI
NMR
Nuclear magnetic resonance
Organic chemistry
Prostate cancer
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Secretion
Zinc
Zinc - chemistry
Zinc transporter
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Summary: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 19F 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. CEST for life: Normal prostate tissue has the highest zinc content in the body. Using TF‐BAPTA as a zinc‐specific iCEST MRI sensor for zinc depletion, a novel imaging biomarker has been developed that may find applications in the early detection of prostate cancer.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201909429