Waerzeggers Yannic, Klein Markus, Miletic Hrvoje, Himmelreich Uwe, Li Hongfeng, Monfared Parisa, Herrlinger Ulrich, Hoehn Mathias, Coenen Heinrich Hubert, Weller Michael, Winkeler Alexandra, Jacobs Andreas Hans
Laboratory for Gene Therapy and Molecular Imagin, Max=Planck Institute for Neurological Research, Cologne, Germany.
Mol Imaging. 2008 Mar-Apr;7(2):77-91.
For clinical application of stem cell-based therapies, noninvasive detection of applied stem cells is of high importance. We report on the feasibility of detecting implanted neural progenitor cells (NPCs) noninvasively and follow their fate and functional status by sequential multimodal molecular imaging and reporter gene technology. We investigated C17.2 cells stably expressing herpes simplex virus type 1-thymidine kinase (HSV-1-tk) and green fluorescent protein (gfp) (C17.2-tkIRESgfp = C17.2-TIG) or HSV-1-tk, gfp, and firefly luciferase (luc) (C17.2-lucIREStkgfp = C17.2-LITG) and determined the detection sensitivity of positron emission tomography (PET) and bioluminescence imaging (BLI) for these cells in culture and in vivo in subcutaneous and intracranial glioma models. In addition, PET and BLI were used to further investigate and follow the fate of implanted C17.2-LITG cells in an intracranial glioma model. We show that both imaging modalities are sensitive in detecting reporter gene expressing NPCs; however, PET, by the use of 9-[4-[(18)F]fluoro-3-hydroxymethyl)butyl]guanine ([(18)F]FHBG), detects NPCs only at sites of disrupted blood-brain barrier. Furthermore, both imaging modalities can be used to detect stem cell fate and migration and indicate excessive proliferation and aberrant migration. In conclusion, multimodal imaging can be used for longitudinal noninvasive monitoring of grafted NPCs in rodents.
对于基于干细胞的疗法的临床应用而言，对所应用的干细胞进行无创检测至关重要。我们报告了通过序贯多模态分子成像和报告基因技术无创检测植入的神经祖细胞（NPCs）并追踪其命运和功能状态的可行性。我们研究了稳定表达单纯疱疹病毒1型胸苷激酶（HSV-1-tk）和绿色荧光蛋白（gfp）的C17.2细胞（C17.2-tkIRESgfp = C17.2-TIG）或HSV-1-tk、gfp和萤火虫荧光素酶（luc）的C17.2细胞（C17.2-lucIREStkgfp = C17.2-LITG），并确定了正电子发射断层扫描（PET）和生物发光成像（BLI）对这些细胞在培养物中以及在皮下和颅内胶质瘤模型体内的检测灵敏度。此外，PET和BLI被用于进一步研究和追踪颅内胶质瘤模型中植入的C17.2-LITG细胞的命运。我们表明，这两种成像方式在检测表达报告基因的NPCs方面都很敏感；然而，PET通过使用9-[4-[(18)F]氟-3-羟甲基)丁基]鸟嘌呤（[(18)F]FHBG），仅在血脑屏障破坏部位检测到NPCs。此外，这两种成像方式都可用于检测干细胞的命运和迁移，并显示过度增殖和异常迁移。总之，多模态成像可用于对啮齿动物体内移植的NPCs进行纵向无创监测。
