Development of new probes for medical imaging of cancer

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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.