Experimental Therapeutics and Molecular Imaging Laboratory, Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Boston, United States.
J Am Chem Soc. 2012 Mar 21;134(11):5149-56. doi: 10.1021/ja209868g. Epub 2012 Mar 7.
We have developed a multifaceted, highly specific reporter for multimodal in vivo imaging and applied it for detection of brain tumors. A metabolically biotinylated, membrane-bound form of Gaussia luciferase was synthesized, termed mbGluc-biotin. We engineered glioma cells to express this reporter and showed that brain tumor formation can be temporally imaged by bioluminescence following systemic administration of coelenterazine. Brain tumors expressing this reporter had high sensitivity for detection by magnetic resonance and fluorescence tomographic imaging upon injection of streptavidin conjugated to magnetic nanoparticles or fluorophore, respectively. Moreover, single photon emission computed tomography showed enhanced imaging of these tumors upon injection with streptavidin complexed to (111)In-DTPA-biotin. This work shows for the first time a single small reporter (∼40 kDa) which can be monitored with most available molecular imaging modalities and can be extended for single cell imaging using intravital microscopy, allowing real-time tracking of any cell expressing it in vivo.
我们开发了一种多功能、高度特异的报告分子，用于多模态活体成像，并将其应用于脑肿瘤的检测。我们合成了一种代谢生物素化的膜结合型海肾荧光素酶，称为 mbGluc-biotin。我们设计了表达这种报告分子的神经胶质瘤细胞，并证实通过系统给予腔肠素，生物发光可实时监测脑肿瘤的形成。通过注射与顺磁纳米颗粒或荧光团偶联的链霉亲和素，表达这种报告分子的脑肿瘤在磁共振和荧光断层成像中的检测具有很高的灵敏度。此外，单光子发射计算机断层扫描显示，注射与（111）In-DTPA-生物素偶联的链霉亲和素后，这些肿瘤的成像得到了增强。这项工作首次表明，一种单一的小报告分子（约 40 kDa）可以通过大多数现有的分子成像方式进行监测，并可通过活体显微镜进行单细胞成像扩展，从而能够实时追踪体内表达该报告分子的任何细胞。
