Nguyen Hung V-T, Chen Qixian, Paletta Joseph T, Harvey Peter, Jiang Yivan, Zhang Hui, Boska Michael D, Ottaviani M Francesca, Jasanoff Alan, Rajca Andrzej, Johnson Jeremiah A
Department of Chemistry, Department of Biological Engineering, Department of Brain and Cognitive Sciences, and Department of Nuclear Science and Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Department of Chemistry, University of Nebraska, Lincoln, Nebraska 68588, United States.
ACS Cent Sci. 2017 Jul 26;3(7):800-811. doi: 10.1021/acscentsci.7b00253. Epub 2017 Jul 12.
Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI . Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field H MRI techniques.
无金属磁共振成像（MRI）造影剂可以克服某些患者群体中与金属基造影剂相关的既定毒性，并实现功能MRI的新模式。在此，我们报告了氮氧化物功能化刷臂星形聚合物有机自由基造影剂（BASP-ORCAs），其克服了与基于氮氧化物的MRI造影剂相关的低对比度和稳定性差的问题。由于其独特的纳米结构，BASP-ORCAs的每氮氧化物横向弛豫率比普通氮氧化物高约44倍，在高度还原环境中具有出色的稳定性，且毒性低。这些特性相结合，使得在全身给药后长达20小时的时间里，小鼠皮下肿瘤中能够积累足够浓度的BASP-ORCA，从而观察到与金属基造影剂相当的MRI对比度。据我们所知，BASP-ORCAs是首批能够使用临床高场H MRI技术进行长时间肿瘤成像的氮氧化物MRI造影剂。
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