Using micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) for trace metal imaging in the development of MRI contrast agents for prostate cancer imaging.

E. Dao, M. V. Clavijo Jordan, K. Geraki, A. Martins, S. Chirayil, A. Sherry, M. Farquharson
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Abstract

BACKGROUND Contrast agents (CA) are administered in magnetic resonance imaging (MRI) clinical exams to measure tissue perfusion, enhance image contrast between adjacent tissues, or provide additional biochemical information in molecular MRI. The efficacy of a CA is determined by the tissue distribution of the agent and its concentration in the extracellular space of all tissues. METHODS In this work, micro-synchrotron radiation x-ray fluorescence (µ-SRXRF) was used to examine and characterize a gadolinium-based zinc-sensitive agent (GdL2) currently under development for detection of prostate cancer (PCa) by MRI. Prostate tissue samples were collected from control mice and mice with known PCa after an MRI exam that included injection of GdL2. The samples were raster scanned to investigate trends in Zn, Gd, Cu, Fe, S, P, and Ca. RESULTS Significant Zn and Gd co-localization was observed in both healthy and malignant tissues. In addition, a marked decrease in Zn was found in the lateral lobe of the prostate obtained from mice with PCa. CONCLUSION We demonstrate here that µ-SRXRF is a useful tool for monitoring the distribution of several elements including Zn and Gd in animal models of cancer. The optimized procedures for tissue preparation, processing, data collection, and analysis are described.
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微同步辐射x射线荧光(µ-SRXRF)在前列腺癌成像MRI造影剂研制中的应用
造影剂(CA)在磁共振成像(MRI)临床检查中用于测量组织灌注,增强相邻组织之间的图像对比度,或在分子MRI中提供额外的生化信息。CA的功效是由药物在组织中的分布及其在所有组织的细胞外空间中的浓度决定的。方法利用微同步辐射x射线荧光(µ-SRXRF)对一种正在开发的用于前列腺癌(PCa) MRI检测的钆基锌敏感剂(GdL2)进行检测和表征。在MRI检查包括注射GdL2后,从对照组小鼠和已知PCa小鼠中收集前列腺组织样本。对样本进行栅格扫描,研究Zn、Gd、Cu、Fe、S、P和ca的变化趋势。结果在健康和恶性组织中均观察到显著的Zn和Gd共定位。此外,前列腺癌小鼠的前列腺外侧叶中锌含量明显降低。结论μ -SRXRF是监测肿瘤动物模型中锌、钆等元素分布的有效工具。对组织制备、处理、数据收集和分析的优化程序进行了描述。
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