Chelator-Free法标记介孔二氧化硅纳米颗粒用于乳腺癌靶向PET成像

Chelator-Free labeling of mesoporous silica nanoparticles for targeted PET imaging of breast cancer

目的 使用Chelator-Free法进行^(68)Ga标记介孔二氧化硅纳米颗粒(MSNs),制备新型正电子发射计算机断层显像(PET)分子探针,并检测其表征、生物安全性、放射性化学性能、体内生物分布及评估其体内乳腺癌靶向PET成像性能。方法 用模板法合成MSNs,对其进行纳米表征及生物安全性分析,明确其良好的生物安全性。并用Chelator-Free法进行^(68)Ga标记,制备出新型纳米PET分子探针^(68)Ga-MSNs,对其进行放射性化学分析,评估其在KM小鼠体内生物分布和对乳腺癌荷瘤小鼠的靶向PET成像性能。结果 MSNs平均粒径为85.03 nm,分散均匀,形貌优良。生物安全性分析显示MSNs在100μg/ml浓度下对细胞增殖无明显影响,显示出良好的生物安全性。^(68)Ga-MSNs的标记率大于95%,放射性化学分析显示,经纯化后^(68)Ga-MSNs放射性化学纯度大于98%,体外标记稳定性优良。KM小鼠体内生物分布显示^(68)Ga-MSNs主要分布于肝脏、脾脏和肺脏。乳腺癌MCF-7荷瘤小鼠模型PET成像表明,^(68)Ga-MSNs在肿瘤部位摄取明显,显示出良好的体内靶向PET成像性能。结论 本研究成功应用Chelator-Free标记法构建的^(68)Ga-MSNs分子探针具有良好的表征、生物安全性及放射性化学性能,具有活体乳腺癌靶向PET成像性能,该研究为乳腺癌的靶向诊疗提供新的药物平台。

Objective To prepare a novel PET nanoprobe based on Chelator-Free Ga labeling of mesoporous silica nanoparticles(MSNs)and evaluate their characterization,biosafety,radiochemical properties,in vivo biodistribution,and breast cancer targeted PET imaging.Methods MSNs were synthesized with the template method.Characterization and biosafety analysis were performed to clarify the good biosafety of MSNs.Chelator-free labeling method was applied to prepare the novel PET nanoprobe Ga-MSNs.Moreover,the radiochemical properties,the distribution of the probe in KM mice,and its targeted PET imaging performance on breast cancer tumor-bearing mice were also evaluated.Results MSNs had uniformly dispersed and excellent morphology with an average diameter of 85.03 nm.Biosafety analysis revealed that MSNs had no significant effect on cell proliferation at a concentration of 100μg/mL,confirming good biosafety of MSNs.The labeling rate of 68Ga-MSNs was greater than 95%.Radiochemical analysis showed that the radiochemical purity of ^(68)Ga-MSNs was greater than 98%after purification and it had high labeling stability in vitro.The biodistribution of ^(68)Ga-MSNs in KM mice demonstrated that the probe was mainly distributed in liver,spleen,and lung.PET imaging performed in the breast cancer MCF-7 tumor-bearing mouse model showed that the uptake of^(68)Ga-MSNs in tumor sites was significantly enriched,indicating favorable breast cancer targeted PET imaging performance in vivo.Conclusions The successfully prepared molecular probe ^(68)Ga-MSNs via Chelator-Free labeling method performs well in its characterization,biosafety,and radiochemical properties,showcasing the potential for targeted PET imaging of breast cancer.The study provides a new drug plaform for targeted diagnosis and treatment of breast cancer.