VALIDATION OF FLUORESCENT DEOXYGLUCOSE (2-NBDG) IN TUMORS

荧光脱氧葡萄糖 (2-NBDG) 在肿瘤中的验证

• 批准号: 7053173
• 负责人: ROGER Gordon O'NEIL
• 金额: $ 12.66万
• 依托单位: 3GEN, LLC
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-19 至 2008-09-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053173
• 关键词: cell line; deoxyglucose; glucose analog; neoplasm /cancer

DESCRIPTION (provided by applicant): A new fluorescent analogue of d-glucose, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG), was recently developed, but has not been characterized as a marker of glucose uptake in cancer cells. Validating this new tracer as a glucose analogue for optical imaging of superficial tumors may have a major impact on clinical and preclinical imaging of superficial tumors. If this new tracer is shown to behave similarly to the 18-fluorine-labeled 2-deoxyglucose (FDG), which is becoming the gold standard for metabolic imaging of tumors by positron-emission topography (PET), we may change the way superficial tumors are detected and diagnosed and produce a low cost screening method for early detection of superficial tumors. This validation may also have a major impact on animal studies since it would be the only glucose analogue validation for metabolic imaging in small animals. The overall goal of the project is to validate first the use of 2-NBDG as a marker of malignant tumor cells (Phase I) and then to develop in vivo methods and fluorescence optical instrumentation, for commercialization, that can be used to\economically monitor 2-NBDG uptake via simple optical instrumentation (Phase II). 2 Specific Aims proposed for Phase I: 1) to assess and characterize the uptake properties of the fluorescent glucose analogue, 2-NBDG, in model malignant tumor cell lines and in normal, non-malignant cells in vitro using fluorescence microscopy and spectrofluorimetry to elucidate the kinetic properties of the 2-NBDG uptake process in selected model malignant tumor cell lines (3 lines) and in normal, non-malignant cells, and 2) to validate the use of the fluorescent glucose analogue, 2-NBDG, as a probe to identify malignant tumor cells by directly comparing the uptake of 2-NBDG with the uptake of radiolabeled 2-dexoyglucose (an established "gold" standard), by radioisotopic analysis, in the same cell lines; and initial uptake in animal tissues. By comparing 2-NBDG uptake with that of the standard, radiolabeled analogue, the use of 2-NBDG as a reliable probe for each cell line will be validated. The end points for assessing successful completion of Phase I is the demonstration of uptake of 2-NBDG in tumor cells comparable to radiolabeled 2-deoxyglocose. Following a successful completion of this phase, we propose to study the feasibility of in-vivo imaging of 2-NBDG in mice models of superficial tumors, and develop instrumentation to detect these tumors non-invasively.

描述（由申请人提供）：d-葡萄糖的新型荧光类似物，2-[N-(7-硝基苯甲-2-氧杂-1,3-二氧醇-4-基)氨基]-2-脱氧葡萄糖 (2-NBDG) ），最近被开发出来，但尚未被定性为癌细胞中葡萄糖摄取的标志物。验证这种新示踪剂作为浅表肿瘤光学成像的葡萄糖类似物可能会对浅表肿瘤的临床和临床前成像产生重大影响。如果这种新的示踪剂被证明与 18-氟标记的 2-脱氧葡萄糖 (FDG) 相似，而 FDG 正在成为正电子发射地形图 (PET) 肿瘤代谢成像的黄金标准，那么我们可能会改变浅表肿瘤的成像方式被检测和诊断并产生用于早期检测浅表肿瘤的低成本筛查方法。该验证也可能对动物研究产生重大影响，因为它将是用于小动物代谢成像的唯一葡萄糖类似物验证。该项目的总体目标是首先验证 2-NBDG 作为恶性肿瘤细胞标记物的用途（第一阶段），然后开发体内方法和荧光光学仪器，以实现商业化，可用于\经济地监测通过简单的光学仪器吸收 2-NBDG（第二阶段）。第一阶段提出的 2 个具体目标： 1) 使用荧光显微镜和荧光分光光度法评估和表征荧光葡萄糖类似物 2-NBDG 在模型恶性肿瘤细胞系和体外正常非恶性细胞中的摄取特性，以阐明选定模型恶性肿瘤细胞系（3 系）和正常非恶性细胞中 2-NBDG 摄取过程的动力学特性，以及 2) 验证荧光的使用葡萄糖类似物 2-NBDG，作为识别恶性肿瘤细胞的探针，通过放射性同位素分析，直接比较同一细胞系中 2-NBDG 的摄取与放射性标记的 2-右旋葡萄糖（既定的“金”标准）的摄取;和动物组织的初始摄取。通过将 2-NBDG 的摄取与标准放射性标记类似物的摄取进行比较，将验证 2-NBDG 作为每种细胞系的可靠探针的用途。评估第一阶段成功完成的终点是证明肿瘤细胞对 2-NBDG 的摄取与放射性标记的 2-脱氧葡萄糖相当。在成功完成这一阶段后，我们建议研究 2-NBDG 在浅表肿瘤小鼠模型中体内成像的可行性，并开发仪器来非侵入性检测这些肿瘤。