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目的:对乳腺癌中IL-11Rα的表达进行非损伤性评价,探讨靶向IL-11Rα的双标造影剂在小鼠种植瘤模型中成像的特异性。方法:采用化学合成的方法合成IL-11的模拟物环九肽,并将其与与近红外染料或近红外/核素染料偶联,进而得到近红外或近红外/核素标记的靶向IL-11Rα的特异性造影剂;首先进行乳腺癌细胞MDA-MB-231的体外结合试验;然后通过建立乳腺癌裸鼠的异体移植瘤模型,进行体内光学成像以及核素成像试验,证实获得的成像化合物在体内试验中的特异性;分析证实获得的成像化合物在体内试验中的特异性;最后病理学检测裸鼠肿瘤标本。结果:体外细胞结合试验证明合成的近红外造影剂能够很好地与人乳腺癌细胞MDA-MB-231相结合。近红外光学成像和核成像均显示了肿瘤的高信号强度,光学成像与核成像结果一致。病理学分析结果证实光学信号较强的组织为乳腺癌组织。结论:靶向IL-11Rα的特异性造影剂可与IL-11Rα阳性的乳腺癌MDA-MB-231细胞特异性结合,并在裸鼠乳腺癌种植模型中进一步证明造影剂在体内成像中的肿瘤特异性,有望为临床肿瘤的早期分子诊断和靶向性治疗提供新的理论基础。
OBJECTIVE: To evaluate the non-invasiveness of IL-11Rα expression in breast cancer and explore the specificity of IL-11Rα-targeted double contrast agent imaging in mouse implanted tumor model. METHODS: The synthetic cyclopentopeptide of IL-11 was synthesized by a chemical synthesis method and coupled with a near-infrared dye or a near-infrared / nuclide dye to obtain a near-infrared or near-infrared / radionuclide labeling target IL-11Rα specific contrast agent; first breast cancer cells MDA-MB-231 in vitro binding assay; and then establish allogeneic xenograft model of breast cancer in nude mice for in vivo optical imaging and radionuclide imaging experiments confirmed that Specificity of imaging compounds in in vivo assays; analysis confirms the specificity of the obtained imaging compounds in in vivo assays; and finally pathological detection of tumor samples in nude mice. Results: In vitro cell-binding experiments demonstrated that the synthesized NIR contrast agent could well bind to human breast cancer cell MDA-MB-231. Near-infrared optical imaging and nuclear imaging both showed high signal intensity of the tumor, and the results of optical imaging and nuclear imaging were consistent. The results of pathological analysis confirmed that the tissue with strong optical signal was breast cancer tissue. CONCLUSIONS: Specific contrast agents that target IL-11Rα specifically bind to IL-11Rα-positive breast cancer MDA-MB-231 cells and further validate the contrast agent in vivo imaging of tumors in a nude mouse breast cancer model of implantation Specificity, is expected to provide a new theoretical basis for early molecular diagnosis and targeted therapy of clinical tumors.