Non-invasive longitudinal imaging of tumor progression using an (111)indium labeled CXCR4 peptide antagonist.
Non-invasive longitudinal imaging of tumor progression using an (111)indium labeled CXCR4 peptide antagonist.
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发表时间：
2012
影响因子：
2.5
通讯作者：
T. Buckle;Nynke S van Berg;J. Kuil;A. Bunschoten;J. Oldenburg;A. Borowsky;J. Wesseling;R. Masada;S. Oishi;N. Fujii;F. V. van Leeuwen
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作者：
T. Buckle;Nynke S van Berg;J. Kuil;A. Bunschoten;J. Oldenburg;A. Borowsky;J. Wesseling;R. Masada;S. Oishi;N. Fujii;F. V. van Leeuwen
趋化因子受体4 （CXCR4）是导管原位癌（DCIS）中过度表达的生物标志物。因此，针对cxcr4的（分子）成像方法可能对这种具有挑战性的癌前病变具有诊断价值。使用铟标记的CXCR4肽拮抗剂（111）in - dtpa - ac - tz14011在类似人DCIS的乳腺上皮内肿瘤生长（MIN-O）小鼠肿瘤模型中观察CXCR4的表达。使用SPET/CT纵向监测MIN-O病变的发展，并将示踪剂的摄取与对照病变的摄取进行比较。免疫组织化学和流式细胞术分析证实了CXCR4的表达。（111）In-DTPA-Ac-TZ14011的摄取与使用（111）In-cDTPA-[RGDfK]的肿瘤血管生成有关。在注射示踪剂24小时后，MIN-O病变可以与低表达cxcr4的对照肿瘤区分开来，而基于α(v)β(3)整合素表达的两种肿瘤的血管生成程度相似。（111） in - dtpa - ac - tz14011在早期MIN-O病变中的摄取明显低于较大的中晚期病变，分别为2.5倍（p=0.03）和7倍（p=0.002）。在免疫组织化学和流式细胞术分析中，中晚期病变显示较高程度的膜性cxcr4染色。从本研究中我们可以得出（111）in - dtpa - ac - tz14011可以纵向显示MIN-O病变中cxcr4的表达。
The chemokine receptor 4 (CXCR4) is a biomarker that is over-expressed in ductal carcinoma in situ (DCIS). Hence, CXCR4-targeted (molecular) imaging approaches may have diagnostic value in such a challenging, premalignant lesion. The indium labeled CXCR4 peptide-antagonist, (111)In-DTPA-Ac-TZ14011, was used to visualize CXCR4-expression in a mammary intraepithelial neoplastic outgrowth (MIN-O) mouse tumor model resembling human DCIS. MIN-O lesion development was longitudinally monitored using SPET/CT and tracer uptake was compared to uptake in control lesions. Expression of CXCR4 was validated using immunohistochemistry and flow cytometric analysis. The uptake of (111)In-DTPA-Ac-TZ14011 was related to tumor angiogenesis using (111)In-cDTPA-[RGDfK]. Twenty-four hours after tracer injection, MIN-O lesions could be discriminated from low CXCR4-expressing control tumors, while the degree of angiogenesis based on the α(v)β(3) integrin expression in both tumor types was similar. The uptake of (111)In-DTPA-Ac-TZ14011 in early MIN-O lesions was significantly lower than in larger intermediate and late-stage lesions, two-and-a-half-times (p=0.03) and seven-times (p=0.002), respectively. Intermediate and late stage lesions show a higher degree of membranous CXCR4-staining at immunohistochemistry and flow cytometric analysis. From this study we can conclude that (111)In-DTPA-Ac-TZ14011 can be used to visualize the CXCR4-expression in MIN-O lesions longitudinally.