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Glucose-Functionalized Liposomes for Reducing False Positives in Cancer Diagnosis

机译:葡萄糖官能化脂质体减少癌症诊断中的假阳性

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Fluorodeoxyglucose-positron emission tomography (F-18-FOG-PET) is a powerful tool for cancer detection, staging, and follow-up. However, F-18-FDG-PET imaging has high rates of false positives, as it cannot distinguish between tumor and inflammation regions that both feature increased glucose metabolic activity. In the present study, we engineered liposomes coated with glucose and the chelator dodecane tetraacetic acid (DOTA) complexed with copper, to serve as a diagnostic technology for differentiating between cancer and inflammation. This liposome technology is based on FDA-approved materials and enables complexation with metal cations and radionuclides. We found that these liposomes were preferentially uptaken by cancer cell lines with high metabolic activity, mediated via glucose transporter-1. In vivo, these liposomes were avidly uptaken by tumors, as compared to liposomes without glucose coating. Moreover, in a combined tumor-inflammation mouse model, these liposomes accumulated in the tumor tissue and not in the inflammation region. Thus, this technology shows high specificity for tumors while evading inflammation and has potential for rapid translation to the clinic and integration with existing PET imaging systems, for effective reduction of false positives in cancer diagnosis.
机译:氟脱氧葡萄糖正电子发射断层扫描(F-18-FOG-PET)是癌症检测、分期和随访的有力工具。然而,F-18-FDG-PET成像的假阳性率很高,因为它无法区分肿瘤和炎症区域,这两个区域都具有增加的葡萄糖代谢活性。在本研究中,我们将葡萄糖和螯合剂十二烷四乙酸(DOTA)与铜复合制成脂质体,作为区分癌症和炎症的诊断技术。这种脂质体技术基于FDA批准的材料,能够与金属阳离子和放射性核素络合。我们发现这些脂质体优先被具有高代谢活性的癌细胞系通过葡萄糖转运蛋白-1介导摄取。在体内,与没有葡萄糖涂层的脂质体相比,这些脂质体被肿瘤贪婪地吸收。此外,在联合肿瘤炎症小鼠模型中,这些脂质体积聚在肿瘤组织中,而不是在炎症区域。因此,这项技术在避免炎症的同时,对肿瘤显示出高度的特异性,并有可能快速转化到临床,并与现有PET成像系统集成,有效减少癌症诊断中的假阳性。

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