Athinoula A. Martines Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA.
Magn Reson Med. 2010 Mar;63(3):617-24. doi: 10.1002/mrm.22216.
One of the key challenges hindering the clinical intervention against brain cancer is defined by the inability to detect brain tumors at an early enough stage to permit effective therapy. Furthermore, the rapid growth and severe lethality of this form of cancer predicate the vital importance of monitoring the development of the pathology and its outcome after therapeutic intervention. With this in mind, we designed a novel membrane-permeant contrast agent, MN-MPAP-Cy5.5, which consists of a superparamagnetic iron oxide core, for MRI conjugated to myristoylated polyarginine peptides, as a membrane translocation module and labeled with the near-infrared dye Cy5.5 for correlative microscopy. This probe showed a remarkable uptake by U-87 human glioma cells in vitro and localized and delineated stereotactically injected tumor in vivo by MRI. Our findings suggest that the agent mediates its effects by translocation of the magnetic nanoparticles label across the leaky tumor vasculature, followed by enhanced accumulation in tumor cells. The noninvasive detection of brain tumors when they are still small represents a formidable challenge from an imaging standpoint. Our study describes an improved strategy to detect brain lesions by utilizing a contrast agent with membrane translocation properties.
阻碍脑癌临床干预的一个关键挑战是，无法在足够早的阶段检测到脑肿瘤，从而无法进行有效的治疗。此外，这种癌症的快速生长和严重致命性使得监测病理发展及其治疗干预后的结果至关重要。考虑到这一点，我们设计了一种新型的膜穿透对比剂 MN-MPAP-Cy5.5，它由超顺磁性氧化铁核心组成，用于与豆蔻酰化多精氨酸肽偶联的 MRI，作为膜转位模块，并标记近红外染料 Cy5.5 用于相关显微镜检查。该探针在体外对 U-87 人神经胶质瘤细胞具有显著的摄取作用，并通过 MRI 对立体定向注射的肿瘤进行定位和描绘。我们的研究结果表明，该试剂通过磁性纳米颗粒标签穿过渗漏的肿瘤血管进行转位来介导其作用，随后在肿瘤细胞中增强积累。从成像的角度来看，当肿瘤还很小时，非侵入性地检测到它们仍然是一个巨大的挑战。我们的研究描述了一种通过利用具有膜转位特性的对比剂来检测脑损伤的改进策略。
