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Development of Ga-68 labeled, biotinylated thiosemicarbazone dextran-coated iron oxide nanoparticles as multimodal PET/MRI probe.
International Journal of Biological Macromolecules ( IF 7.7 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.ijbiomac.2020.01.208
Nazila Gholipour 1 , Mehdi Akhlaghi 2 , Amin Mokhtari Kheirabadi 2 , Parham Geramifar 2 , Davood Beiki 2
Affiliation  

Bifunctional biotinylated thiosemicarbazone dextran-coated iron oxide Nanoparticles (NPs) were fabricated. Aldehyde groups of the oxidized dextran-coating layer were utilized to conjugate biotin as a tumor-targeting agent and thiosemicarbazide as a cation chelator on the surface of NPs. The final product was characterized for physicochemical and biological properties. It was compatible with red blood cells and did not change the blood coagulation time. It also showed a significantly enhanced affinity to biotin receptor-positive 4T1 cells compared to non-biotinylated ones. The r2 relaxivity coefficient value of the final product was 110.2 mM-1 s-1. Although biotinylated NPs were easily radiolabeled with Ga-68 at room temperature, the stable radiolabeled NPs were achieved at a higher temperature (60 °C). The radiolabeled NPs were majorly accumulated in the liver and spleen. However, about 5.4% ID/g of the radiolabeled NPs was accumulated within the 4T1 tumor site. Blocking studies was performed by the biotin molecules pre-injection showed uptake reduction in the 4T1 tumor (about 1.1% ID/g). The radiolabeled NPs could be used for the early detection of biotin receptor-positive tumors via PET-MRI.

中文翻译:

Ga-68标记的生物素化硫代半碳素葡聚糖涂层氧化铁纳米粒子的开发,作为多峰PET / MRI探针。

制备了双功能生物素化的硫代半碳素葡聚糖涂层的氧化铁纳米粒子(NPs)。氧化的右旋糖酐涂层的醛基用于在NPs表面偶联生物素作为肿瘤靶向剂和硫代氨基脲作为阳离子螯合剂。对最终产物进行理化和生物学特性表征。它与红细胞相容,并且不改变凝血时间。与未生物素化的细胞相比,它还显示出对生物素受体阳性4T1细胞的显着增强的亲和力。最终产物的r2弛豫系数值为110.2mM-1s-1。尽管在室温下用Ga-68可以轻松地对生物素化的NPs进行放射性标记,但在更高的温度(60°C)下可以获得稳定的放射性标记的NPs。放射性标记的NP主要在肝和脾中积累。但是,约5.4%ID / g的放射性标记NPs积累在4T1肿瘤部位内。通过生物素分子预注射进行的阻断研究显示4T1肿瘤的摄取减少(约1.1%ID / g)。放射性标记的NP可用于通过PET-MRI早期检测生物素受体阳性的肿瘤。
更新日期:2020-01-23
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