Development of new probes for medical imaging of cancer

测量了植入C3H小鼠股骨皮下的酞菁锂(LiPc)的ESR谱线宽度。碳束(13keV/μm，20Gy)照射小鼠双腿数小时后，线宽增加，而对照组小鼠无明显增加。这种升高是指照射后组织中的氧分压升高。LiPc植入股骨区肿瘤组织(RIF-1)的线宽小于正常组织(RIF-1)，表明肿瘤组织的氧分压低于正常组织。在谷胱甘肽或NADPH存在下，超氧阴离子自由基对吡咯烷基氮氧自由基(PROXYL)的ESR信号降低幅度远小于哌啶氮氧自由基(TEMPO)，提示PROXYL是一种更好的测量组织还原代谢的探针。还原代谢率可作为生存能力的一项指标。给荷瘤小鼠静脉注射3-羟甲基-2，2，5，5-四甲基吡咯烷-N-氧基(羟甲基-丙氧基)。在肿瘤区域测得的ESR信号衰减相对较慢(t_&lt；1/2&gt；=约25min)，在LiPc移植的肿瘤组织进行ESR成像后，注射羟甲基代理，然后获得羟甲基丙氧基的ESR图像。这项技术使得获得同一动物体内两种不同探针的图像成为可能。通过进一步开发成像软件，部分氧分压和代谢还原活动的同时成像可能成为可能。

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.