The quest for nanomaterial-based imaging probes that can provide positive contrast in MRI is fueled by the necessity of developing novel diagnostic applications with potential for clinical translation that current gold standard probes cannot provide. Although interest in nanomaterials for positive contrast has increased in recent years, their study is less developed than that of traditional negative contrast probes in MRI. In our search for new magnetic materials with enhanced features as positive contrast probes for MRI, we decided to explore the chemical space to comprehensively analyze the effects of different metals on the performance of iron oxide nanomaterials already able to provide positive contrast in MRI. To this end, we synthesized 30 different iron oxide-based nanomaterials. Thorough characterization was performed, including multivariate analysis, to study the effect of different variables on their relaxometric properties. Based on these results, we identified the best combination of metals for in vivo imaging and tested them in different experiments. First, we tested its performance on magnetic resonance angiography using a concentration ten times lower than that clinically approved for Gd. Finally, we studied the capability of these nanomaterials to cross the affected blood–brain barrier in a glioblastoma model. The results showed that the selected nanomaterials provided excellent positive contrast at large magnetic field and were able to accumulate at the tumor site, highlighting the affected tissue.

中文翻译：

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增强 MRI 阳性对比和胶质母细胞瘤体内摄取的元素周期表筛选

开发新型诊断应用的必要性推动了人们对能够在 MRI 中提供正对比度的基于纳米材料的成像探针的需求，这些应用具有当前金标准探针无法提供的临床转化潜力。尽管近年来人们对用于正对比的纳米材料的兴趣有所增加，但与 MRI 中传统的负对比探针相比，他们的研究进展较少。在寻找具有增强功能的新型磁性材料作为 MRI 正对比探针时，我们决定探索化学空间，以全面分析不同金属对已经能够在 MRI 中提供正对比的氧化铁纳米材料性能的影响。为此，我们合成了 30 种不同的氧化铁基纳米材料。进行了全面的表征，包括多变量分析，以研究不同变量对其弛豫特性的影响。根据这些结果，我们确定了用于体内成像的最佳金属组合，并在不同的实验中对其进行了测试。首先，我们使用比临床批准的 Gd 浓度低十倍的浓度测试其在磁共振血管造影中的性能。最后，我们研究了这些纳米材料在胶质母细胞瘤模型中穿过受影响的血脑屏障的能力。结果表明，所选的纳米材料在大磁场下提供了优异的正对比度，并且能够在肿瘤部位积聚，突出受影响的组织。