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用于多模态断层成像检测硬癌型胃癌的聚合物胶束平台

Polymeric Micelle Platform for Multimodal Tomographic Imaging to Detect Scirrhous Gastric Cancer.

作者信息

Miura Yutaka, Tsuji Atsushi B, Sugyo Aya, Sudo Hitomi, Aoki Ichio, Inubushi Masayuki, Yashiro Masakazu, Hirakawa Kosei, Cabral Horacio, Nishiyama Nobuhiro, Saga Tsuneo, Kataoka Kazunori

机构信息

Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Diagnostic Imaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.

出版信息

ACS Biomater Sci Eng. 2015 Nov 9;1(11):1067-1076. doi: 10.1021/acsbiomaterials.5b00142. Epub 2015 Oct 1.

Abstract

Scirrhous gastric cancer (SGC) is a recalcitrant tumor, which is among the most lethal cancers. A critical issue for the improvement of SGC prognosis is the lack of an effective imaging method for accurate detection and diagnosis. Because combined nuclear medicine imaging with magnetic resonance imaging (MRI) has the ability to detect cancer with high sensitivity, and quantitation and spatial resolution, it has potential to overcome the issues with SGC detection. Herein, we designed and synthesized a new block copolymer poly(ethylene glycol)--poly(γ-benzyl l-glutamate) linked with a chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-PEG--PBLG) to provide a platform for multimodal tomographic imaging. We then successfully prepared DOTA-functionalized polymeric micelles (DOTA/m) measuring 30 nm in diameter, which is an appropriate size to penetrate deeply into tumors with thick fibrosis, including SGC. In-labeled DOTA/m highly accumulated in Colon-26 tumors (mouse colon cancer with hyperpermeability), but also in OCUM-2 M LN tumors (SGC with hypopermeability), clearly depicting both tumors by single photon emission computed tomography (SPECT). Gd-labeled DOTA/m clearly visualized OCUM-2 M LN tumors by MRI with high spatial resolution. Moreover, In/Gd-labeled micelles, as well as the mixture of In- and Gd-labeled DOTA/m demonstrated the capability of this system for selective multimodal SPECT/MR imaging of SCG. Our findings support In/Gd-DOTA-labeled micelles as a clinical translationable modality for multimodal tomographic imaging capable of detecting SGC.

摘要

硬癌性胃癌(SGC)是一种难治性肿瘤,是最致命的癌症之一。改善SGC预后的一个关键问题是缺乏有效的成像方法来进行准确检测和诊断。由于核医学成像与磁共振成像(MRI)相结合具有高灵敏度、定量和空间分辨率的癌症检测能力,因此有潜力克服SGC检测中的问题。在此,我们设计并合成了一种新的嵌段共聚物聚(乙二醇)-聚(γ-苄基-L-谷氨酸),其与螯合剂1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA-PEG-PBLG)相连,以提供多模态断层成像平台。然后,我们成功制备了直径为30 nm的DOTA功能化聚合物胶束(DOTA/m),该尺寸适合深入渗透到包括SGC在内的具有厚纤维化的肿瘤中。In标记的DOTA/m在Colon-26肿瘤(具有高通透性的小鼠结肠癌)中高度积累,但在OCUM-2 M LN肿瘤(具有低通透性的SGC)中也有积累,通过单光子发射计算机断层扫描(SPECT)清晰地描绘了这两种肿瘤。Gd标记的DOTA/m通过MRI以高空间分辨率清晰地显示了OCUM-2 M LN肿瘤。此外,In/Gd标记的胶束以及In标记和Gd标记的DOTA/m的混合物证明了该系统对SGC进行选择性多模态SPECT/MR成像的能力。我们的研究结果支持In/Gd-DOTA标记的胶束作为一种可临床转化的多模态断层成像模式,能够检测SGC。

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