Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Neoplasia. 2014 May;16(5):432-40. doi: 10.1016/j.neo.2014.05.005. Epub 2014 Jun 23.
New intravital optical imaging technologies have revolutionized our understanding of mammalian biology and continue to evolve rapidly. However, there are only a limited number of imaging probes available to date. In this study, we investigated in mouse models of glioblastoma whether a fluorescent small molecule inhibitor of the DNA repair enzyme PARP1, PARPi-FL, can be used as an imaging agent to detect glioblastomas in vivo. We demonstrated that PARPi-FL has appropriate biophysical properties, low toxicity at concentrations used for imaging, high stability in vivo, and accumulates selectively in glioblastomas due to high PARP1 expression. Importantly, subcutaneous and orthotopic glioblastoma xenografts were imaged with high contrast clearly defining tumor tissue from normal surrounding tissue. This research represents a step toward exploring and developing PARPi-FL as an optical intraoperative imaging agent for PARP1 in the clinic.
新的活体光学成像技术彻底改变了我们对哺乳动物生物学的理解，并在持续快速发展。然而，迄今为止，可用的成像探针数量有限。在本研究中，我们在胶质母细胞瘤的小鼠模型中研究了一种荧光小分子 PARP1 抑制剂 PARPi-FL 是否可作为成像剂用于体内检测胶质母细胞瘤。我们证明了 PARPi-FL 具有适当的物理化学特性，在用于成像的浓度下具有低毒性，在体内具有高稳定性，并且由于 PARP1 表达水平高而选择性地在胶质母细胞瘤中积累。重要的是，皮下和原位胶质母细胞瘤异种移植瘤的对比度高，可清晰地将肿瘤组织与正常周围组织区分开来。这项研究代表了朝着探索和开发 PARPi-FL 作为 PARP1 的光学术中成像剂在临床上的应用迈出的一步。
