Nanoreporter PET predicts the efficacy of anti-cancer nanotherapy.
Nanoreporter PET predicts the efficacy of anti-cancer nanotherapy.
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DOI：
10.1038/ncomms11838
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发表时间：
2016-06-20
影响因子：
16.6
通讯作者：
Reiner T
中科院分区：
文献类型：
--
作者：
Pérez-Medina C;Abdel-Atti D;Tang J;Zhao Y;Fayad ZA;Lewis JS;Mulder WJM;Reiner T
纳米粒药物制剂的应用，如纳米脂质体阿霉素（Doxil），越来越多地整合在临床癌症护理中。尽管纳米医学在过去三十年中具有显着的潜力和增长，但其对癌症患者的临床益处各不相同。在这里，我们报告了一种非侵入性定量正电子发射断层扫描（PET）纳米报告技术，可预测个体受试者的治疗结果。在乳腺癌小鼠模型中，我们证明了共注射Doxil和锆-89纳米报告分子（89 Zr-NRep）可以精确定量多柔比星（DOX）。重要的是，89 Zr-NRep的摄取也与其他类型的纳米颗粒的肿瘤积累相关。89 Zr-NRep PET成像显示显著的蓄积异质性，与肿瘤大小无关。我们随后证明，肿瘤中DOX累积>25 mg kg−1的小鼠具有显著更好的生长抑制和增强的存活率。这种非侵入性成像工具可能会发展成为一个强大的纳入标准，适合患者的纳米治疗。 纳米颗粒药物制剂目前被用作癌症治疗，但患者的反应是高度可变的。在这里，作者开发了一种锆-89纳米报告物，能够使用PET预测抗癌纳米颗粒药物制剂在小鼠乳腺癌模型中共注射时的治疗积累和疗效。
The application of nanoparticle drug formulations, such as nanoliposomal doxorubicin (Doxil), is increasingly integrated in clinical cancer care. Despite nanomedicine's remarkable potential and growth over the last three decades, its clinical benefits for cancer patients vary. Here we report a non-invasive quantitative positron emission tomography (PET) nanoreporter technology that is predictive of therapeutic outcome in individual subjects. In a breast cancer mouse model, we demonstrate that co-injecting Doxil and a Zirconium-89 nanoreporter (89Zr-NRep) allows precise doxorubicin (DOX) quantification. Importantly, 89Zr-NRep uptake also correlates with other types of nanoparticles' tumour accumulation. 89Zr-NRep PET imaging reveals remarkable accumulation heterogeneity independent of tumour size. We subsequently demonstrate that mice with >25 mg kg−1 DOX accumulation in tumours had significantly better growth inhibition and enhanced survival. This non-invasive imaging tool may be developed into a robust inclusion criterion for patients amenable to nanotherapy. Nanoparticle drug formulations are currently used as cancer treatment but the response in patients is highly variable. Here, the authors developed a Zirconium-89 nanoreporter able to predict using PET, therapeutic accumulation and efficacy of anti-cancer nanoparticle drug formulations when co-injected in a murine breast cancer model.