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Development of new probes for medical imaging of cancer

开发用于癌症医学成像的新探针

基本信息

批准号：
13672268
负责人：
TAKESHITA Keizo
金额：
$ 1.92万
依托单位：
National Institute of Radiological Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672268/
关键词：
partial oxygen Dressure in vivo ESR lithium phthalocyanine nitroxyl radical redox ESR-CT 酸素分圧

项目摘要

ESR line width of lithium phthalocyanine (LiPc) implanted subcutaneously in the femoral region of C3H mice was measured. The line width increased a few hours after irradiation of the legs of the mice with carbon beam (13 keV/μm, 20 Gy), while no increase was observed for control mice. This increase means the increase of partial oxygen pressure in the tissues after the irradiation. The line width of LiPc implanted in the tumor tissue (RIF-1) at femoral region was smaller than that in normal tissue, indicating the low partial oxygen pressure in the tumor tissue comparing with the normal tissue.ESR signal reduction of pyrrolidine nitroxyl (PROXYL) caused by superoxide radical in the presence of glutathione or NADPH was much smaller than that of piperidine nitroxyl (TEMPO), suggesting that PROXYL is a better probe for the measurement of reductive metabolism in tissue. The reductive metabolism may be used as an index of viability. 3-Hydroxymethyl-2, 2, 5, 5-tetramethylpyrrolidine-N-oxyl (hydroxymethyl-PROXYL) was intravenously injected to tumor-bearing mouse. ESR signal decay measured at tumor region was relatively slow (t_<1/2>=about 25 min).Hydroxymethyl-PROXY was injected after ESR imaging of LiPc implanted tumor tissue, and then ESR image of hydroxymethyl-PROXYL was obtained. This technique made possible obtaining the images of two different probes in the same animal. Simultaneous imaging of partial oxygen pressure and metabolic reduction activity may become possible by further development of imaging software.

测定了C_3H小鼠股骨皮下植入酞菁锂（LiPc）的ESR谱线宽度。用碳束（13 keV/μm，20戈伊）照射小鼠的腿后数小时，谱线宽度增加，而对照小鼠没有观察到谱线宽度增加。这种增加意味着照射后组织中氧分压的增加。肿瘤组织（RIF-1）股部植入的LiPc的线宽小于正常组织，表明肿瘤组织的氧分压较正常组织低，在谷胱甘肽或NADPH存在下，超氧自由基引起的吡咯烷硝酰基（PROXYL）ESR信号降低远小于哌啶硝酰基（克里思），表明PROXYL是测量组织中还原代谢的更好探针。还原代谢可用作生存力的指标。将3-羟甲基-2，2，5，5-四甲基吡咯烷-N-氧基（羟甲基-PROXYL）静脉注射至荷瘤小鼠。肿瘤区ESR信号衰减较慢（t <1/2>= 25 min左右），植入肿瘤组织后，注射羟甲基PROXY，获得羟甲基PROXYL的ESR图像。该技术使得在同一动物中获得两种不同探针的图像成为可能。通过进一步开发成像软件，氧分压和代谢还原活性的同时成像可能成为可能。