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 expression of IL-11Rα in breast cancer noninvasively,and investigate the specificity of dual-labeled IL-11Rα-specific targeted in the imaging of breast cancer xenograft model.Methods: Peptide based IL-11Rα imaging agents were synthesized and labeled with near-infrared dye or nuclides for vitro cell binding studies on breast cancer cell line MDA-MB-231.A xenograft model was established,and in vivo optical imaging studies as well as nuclear imaging were carried out with near-infrared /nuclides imaging agent,the high signal specimen of mice was analyzed pathologically to further verify the imaging results.Results:Cell binding studies demonstrated those agents bound to the human breast cancer cells MDA-MB-231 which were IL-11Rα positive.Near infrared optical imaging and nuclear imaging showed the high signal intensity in tumor with one accord.Pathological results proved that the high signal specimen was indeed breast cancer tissue.Conclusion:IL-11Rα specific imaging agents could bind to the IL-11Rα positive cancer,also image specificity xenograft in the model of breast cancer.It may provide the theoretical foundation for the early molecular diagnosis of the tumor and its targeted therapy.