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）：一种新的D-葡萄糖的荧光类似物，2- [N-（7-硝基苯甲酸氧化氢）-1,3-二氧酚-4-基-4-基）氨基] -2-脱氧葡萄糖（2-nbdg），最近是最近开发的，但并未以癌细胞为glucose uptake细胞的标记。验证这种新的示踪剂作为浅表肿瘤的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。如果证明这款新示踪剂的行为与18-氟标记的2-脱氧葡萄糖（FDG）相似，该示射剂（FDG）已成为正电子发射地形图（PET）代谢成像的黄金标准，我们可能会改变检测和诊断和诊断和诊断出低成本筛选的早期摄影方法的表面肿瘤的方式。这种验证也可能对动物研究产生重大影响，因为它将是唯一用于小动物代谢成像的葡萄糖模拟验证。该项目的总体目标是首先验证2-nbdg作为恶性肿瘤细胞的标志（I阶段），然后在体内方法和荧光光学仪器中开发用于商业化，可用于通过简单的光学仪器（II阶段II）进行经济上监测2-NBDG的吸收。 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,非恶性细胞和2）通过直接比较2-NBDG的摄取与摄取2-nbdg的摄取与摄取radiolabel的2-脱甲基葡萄糖（通过既定的“金牌”标准），通过放射性分析细胞分析，以验证荧光葡萄糖模拟2-NBDG的使用2-NBDG，以鉴定恶性肿瘤细胞；和动物组织中的初始摄取。通过将2-nBDG摄取与标准标记的类似物的摄取进行比较，将验证2-nbdg作为可靠的探针的使用。评估成功完成I期的终点是肿瘤细胞中2-nbdg的摄取的证明，可与放射性标记的2-脱氧核糖相媲美。成功完成此阶段后，我们建议研究2-NBDG在浅表肿瘤模型中的体内成像的可行性，并开发仪器以非侵入性地检测这些肿瘤。