Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging
Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging
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DOI：
10.1073/pnas.1423021112
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发表时间：
2015-05-26
影响因子：
11.1
通讯作者：
Yang, Jenny J.
中科院分区：
文献类型：
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作者：
Xue, Shenghui;Yang, Hua;Yang, Jenny J.
利用现有的 MRI 技术，由于缺乏无 Gd3+ 毒性的高灵敏度造影剂，与高死亡率和治疗反应差相关的原发性和转移性肝癌只能在晚期才能诊断出来。我们开发了一种蛋白质造影剂 (ProCA32)，与现有造影剂相比，它对 Gd3+ 表现出高稳定性，对 Gd3+ 的选择性比 Zn2+ 高 10(11) 倍。 ProCA32由小清蛋白修饰而成，具有高弛豫率（r(1)/r(2)：每个颗粒66.8 mmol(-1).s(-1)/89.2 mmol(-1).s(-1)）。使用 T-1 和 T-2 加权以及 T-2/T-1 比率成像，我们首次（据我们所知）实现了对直径小至 0.24 毫米的早期肝转移的稳健 MRI 检测，远小于当前 10-20 毫米的检测极限。此外，ProCA32 对肝窦空间和药代动力学表现出适当的体内偏好，以实现高质量成像。 ProCA32对于原发性和转移性肝癌的无创早期检测以及监测治疗和指导治疗干预（包括药物输送）具有不可估量的价值。
With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 10(11)-fold greater selectivity for Gd3+ over Zn2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r(1)/r(2): 66.8 mmol(-1).s(-1)/89.2 mmol(-1).s(-1) per particle). Using T-1-and T-2-weighted, as well as T-2/T-1 ratio imaging, we have achieved, for the first time (to our knowledge), robustMRI detection of early liver metastases as small as similar to 0.24 mm in diameter, much smaller than the current detection limit of 10-20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.