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一种新型铃兰花香型磁共振和荧光双模态对比剂用于前列腺癌细胞成像。

A novel lily-of-the-valley fragrance contrast agent for magnetic resonance and fluorescence imaging of prostate cancer cells.

机构信息

Department of Neuroradiology, Molecular Imaging Laboratory, University of Tubingen, Hoppe-Seyler-Str.3, 72076 Tubingen, Germany.

出版信息

Curr Pharm Biotechnol. 2012 Feb;13(2):373-7. doi: 10.2174/138920112799095374.

Abstract

Detection of prostate carcinoma metastases is currently performed either via indirect tests like the prostate specific antigen (PSA) or prostate cancer gene 3 (PCA3) or by biopsies from masses found with medical imaging methods. Our goal was to use an ectopic odorant receptor to target prostate-derived cells throughout the body for imaging by magnetic resonance and fluorescence imaging. We synthesized a conjugate containing undecylic aldehyde (an antagonist of the human olfactory receptor hOR17-4), gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (a common magnetic resonance contrast agent) and fluorescein isothiocyanate (a fluorescent dye). Two different prostate cancer cell lines as well as five other different malignant cell lines and healthy prostate epithelial cells were incubated with this conjugate and evaluated by flow cytometry, confocal laser scanning microscopy and magnetic resonance imaging. The prostate- derived healthy and malignant cells showed stronger fluorescence than the non-prostate cancer cell lines in the flow cytometry and confocal laser scanning microscopy experiments. In the magnetic resonance imaging experiments the T1 relaxation time reduction (higher signal intensity) was also stronger for the prostate-derived cells than for the non-prostate cells. The examined conjugate showed high prostate-cell-specificity. This property makes it of potential value in the diagnosis of prostate cancer lymph node metastases.

摘要

目前,前列腺癌转移的检测要么通过间接测试,如前列腺特异性抗原(PSA)或前列腺癌基因 3(PCA3),要么通过对医学成像方法发现的肿块进行活检来进行。我们的目标是使用异位气味受体来靶向全身前列腺来源的细胞,通过磁共振和荧光成像进行成像。我们合成了一种包含十一醛(人类嗅觉受体 hOR17-4 的拮抗剂)、钆-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(一种常见的磁共振对比剂)和异硫氰酸荧光素(一种荧光染料)的缀合物。将两种不同的前列腺癌细胞系以及其他五种不同的恶性细胞系和健康的前列腺上皮细胞与该缀合物孵育,并通过流式细胞术、共聚焦激光扫描显微镜和磁共振成像进行评估。在流式细胞术和共聚焦激光扫描显微镜实验中,前列腺来源的健康和恶性细胞的荧光强度明显强于非前列腺癌细胞系。在磁共振成像实验中,前列腺来源的细胞的 T1 弛豫时间缩短(信号强度更高)也明显强于非前列腺细胞。该检测的缀合物显示出高度的前列腺细胞特异性。这种特性使其在前列腺癌淋巴结转移的诊断中具有潜在的价值。

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