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.
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.
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DOI：
10.1021/acs.inorgchem.9b01132
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发表时间：
2019-10-21
影响因子：
4.6
通讯作者：
Sherry, A. Dean
中科院分区：
文献类型：
--
作者：
Jordan, Veronica Clavijo;Al-Ebraheem, Alia;Geraki, Kalotina;Dao, Erica;Martins, Andre F.;Chirayil, Sara;Farquharson, Michael;Sherry, A. Dean
前列腺锌含量是用于区分正常健康组织与良性前列腺增生（BPH）和前列腺癌（PCa）的已知生物标志物。鉴于锌含量不容易测量，没有组织活检，我们一直在探索非侵入性成像方法，以检测这些诊断差异使用锌响应MRI造影剂。在小鼠的成像研究中，我们观察到葡萄糖推注刺激禁食小鼠前列腺分泌锌。这一发现允许使用基于Gd的锌传感器来检测PCa转基因腺癌小鼠模型中健康与恶性前列腺组织区域中的差异锌分泌。在这里，我们使用了一种锌响应MRI试剂来检测恶性肿瘤发展过程中前列腺中锌的释放，并通过同步辐射X射线荧光（μSR-XRF）确认总组织锌的损失。定量μSR-XRF结果表明，小鼠前列腺的侧叶独特地积累了高浓度的锌，1.06 ± 0.08 mM，并且前列腺中锌含量的已知损失仅在PCa发育期间的侧叶中观察到。此外，本发明还我们证实，通过锌分泌丧失识别的病变确实代表恶性肿瘤，并且病变中的相对锌浓度降低至0.370 ± 0.001 mM。μSR-XRF数据还通过显示葡萄糖促进锌池（~1 mM）的移动，提供了对锌分泌机制的见解。从小鼠前列腺外侧叶的腺腔进入腺体周围的基质/平滑肌。通过μSR-XRF检测到的锌和钆在基质/平滑肌区域中的共定位证实，葡萄糖启动锌从细胞内隔室分泌到腺体的细胞外间隙中，在细胞外间隙中锌与Gd基试剂和白蛋白结合，促进MR图像增强。
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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影响因子：
62.1
作者：
Wahsner J;Gale EM;Rodríguez-Rodríguez A;Caravan P
通讯作者：
Caravan P
影响因子：
5.5
作者：
Pace NJ;Weerapana E
通讯作者：
Weerapana E
DOI：
10.1111/j.1750-3639.2009.00283.x
发表时间：
2010-03
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Lyubartseva G;Smith JL;Markesbery WR;Lovell MA
通讯作者：
Lovell MA
DOI：
10.1073/pnas.1109649108
发表时间：
2011-11-08
影响因子：
11.1
作者：
Lubag, Angelo J. M.;De Leon-Rodriguez, Luis M.;Sherry, A. Dean
通讯作者：
Sherry, A. Dean
影响因子：
15
作者：
Martins, Andre F.;Jordan, Veronica Clavijo;Sherry, A. Dean
通讯作者：
Sherry, A. Dean