HAP-Multitag, a PET and Positive MRI Contrast Nanotracer for the Longitudinal Characterization of Vascular Calcifications in Atherosclerosis,ACS Applied Materials & Interfaces

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HAP-Multitag, a PET and Positive MRI Contrast Nanotracer for the Longitudinal Characterization of Vascular Calcifications in Atherosclerosis
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2021-09-16 , DOI: 10.1021/acsami.1c13417
Juan Pellico _{1,

2} , Irene Fernández-Barahona _{3,

4} , Jesús Ruiz-Cabello _{1,

3,

5,

6} , Lucía Gutiérrez ₇ , María Muñoz-Hernando _{4,

8} , María J Sánchez-Guisado ₅ , Irati Aiestaran-Zelaia ₅ , Lydia Martínez-Parra ₅ , Ignacio Rodríguez _{1,

3} , Jacob Bentzon ₈ , Fernando Herranz _{1,

4}

Affiliation

Vascular microcalcifications are associated with atherosclerosis plaque instability and, therefore, to increased mortality. Because of this key role, several imaging probes have been developed for their in vivo identification. Among them, [¹⁸F]FNa is the gold standard, showing a large uptake in the whole skeleton by positron emission tomography. Here, we push the field toward the combined anatomical and functional early characterization of atherosclerosis. For this, we have developed hydroxyapatite (HAP)-multitag, a bisphosphonate-functionalized ⁶⁸Ga core-doped magnetic nanoparticle showing high affinity toward most common calcium salts present in microcalcifications, particularly HAP. We characterized this interaction in vitro and in vivo, showing a massive uptake in the atherosclerotic lesion identified by positron emission tomography (PET) and positive contrast magnetic resonance imaging (MRI). In addition, this accumulation was found to be dependent on the calcification progression, with a maximum uptake in the microcalcification stage. These results confirmed the ability of HAP-multitag to identify vascular calcifications by PET/(T₁)MRI during the vulnerable stages of the plaque progression.

中文翻译：

HAP-Multitag，一种 PET 和阳性 MRI 对比纳米示踪剂，用于动脉粥样硬化中血管钙化的纵向表征

血管微钙化与动脉粥样硬化斑块的不稳定性有关，因此会增加死亡率。由于这一关键作用，已经开发了几种成像探针用于体内鉴定。其中，[ ¹⁸ F]FNa 是金标准，正电子发射断层扫描显示在整个骨骼中大量摄取。在这里，我们将这一领域推向了动脉粥样硬化的联合解剖学和功能性早期表征。为此，我们开发了羟基磷灰石 (HAP)-多标签，这是一种双膦酸盐功能化的⁶⁸ Ga 核掺杂磁性纳米颗粒，对微钙化中存在的大多数常见钙盐，特别是 HAP 具有高亲和力。我们在体外表征了这种相互作用，并在体内，显示通过正电子发射断层扫描 (PET) 和正对比磁共振成像 (MRI) 确定的动脉粥样硬化病变中的大量摄取。此外，发现这种积累依赖于钙化进程，在微钙化阶段吸收最大。这些结果证实了 HAP-multitag在斑块进展的脆弱阶段通过 PET/(T _{1 )MRI 识别血管钙化的能力。}

更新日期：2021-09-29

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