| Objective:1.To study the expression of CXCR4 and uptake of 99mTc-AMD3100 in four different lung cancer cell lines; 2.To study the biodistribution in viro and SPECT imaging of 99mTc-AMD3100 in tumor-bearing mice; 3.To study the comparison between 99mTc-AMD3100 and other tracers on biodistribution and imaging in tumor-bearing mice and inflammatary mice.Methods:1.We firstly detected the CXCR4 expression in A549,H460,95D and GLC80 cells by immunofluorescence and RT-PCR; Then we measured 99mTc-AMD3100 radioactive uptake in cells at different time; At last we analyzed the relevance between CXCR4 expression and 99mTc-AMD3100 uptake.2.We studied the biodistribution of 99mTc-AMD3100 in NH mice. Then tumor-bearing mice were performed SPECT imaging at different time, we measured the biodistribution of 99mTc-AMD3100 in blood, heart, liver, spleen, lung, kidney, muscle. The biodistribution in different tumor-bearing mice at best imaging time were compared. Then CXCR4 expression were detected in tumor by Western-Blot, we analyzed the relevance between CXCR4 expression and 99mTc-AMD3100 uptake.3.15 tumor-bearing mice were divided into AMD3100, FDG and FLT groups. We compared the biodistribution of the 3 tracers in tumor-bearing mice. 15 inflammatory mice were divided into AMD3100, FDG and FLT groups. We compared the drug biodistribution of the 3 tracers in inflammatory mice.Results:1.CXCR4 expresssion were significantly different among the four cell lines by immunofluorescence and RT-PCR, the successive order was A549, H460, 95D, GLC80.99mTc-AMD3100 uptake of the four cells at each time were different. The uptake hit high at 2h. There was positive relevance between 99mTc-AMD3100 uptake and CXCR4 expression.2.The biodistribution of 99mTc-AMD3100 in NH mice showed:blood clearance was quick and radioativity mainly concentrated in liver, spleen, kidney, but less concentrated in heart, lung, muscle. At 4h, the tumor of A549 mice took on an clear image, H460 mice took on weaker one, and there was no image in 95D and GLC80 mice. There was significant difference of tumor radioactivity among each group, except for 95D and GLC80 group. CXCR4 expresssion had same trendency towards the tumor radioactive uptake, but there was no obvious relevance.3.Tumor in FDG and FLT mice imaged clearly at 60min p.i. In FDG group, except for heart and kidney, the ratios of tumor/other tissues were above 2. In FLT group, except for kidney, spleen and liver, the ratios of tumor/other tissues were above 2. The ratios of tumor/heart, tumor/liver, tumor/spleen and tumor/kidney beween FDG and AMD3100 group were significantly different. The ratios of tumor/blood, tumor/liver and tumor/kidney beween FLT and AMD3100 group were significantly different. The inflammation tissues were not visible in 99mTc-AMD3100 SPECT and 18F-FLT PET imaging and were visible in 18F-FDG PET imaging. In AMD3100 and FLT group, the ratios of inflammation/blood and inflammation/muscle were under 2. In FDG group, the ratios of inflammation/blood and inflammation/muscle were above 2. There was significant difference between FDG and AMD3100 group on the ratios of inflammation/blood and inflammation/muscle; There was no significant difference between 18F-FLT and 99mTc-AMD3100 on the ratios of inflammation/blood and inflammation/muscle.Conclusions:In vitro, the uptake of 99mTc-AMD3100 in different cells had positive linear correlation with the expression of CXCR4.99mTc-AMD3100 presented image in A549 and H460 mice, which combinning with the biodistribution trait of 99mTc-AMD3100 in vivo suggested that 99mTc-AMD3100 is significative to lung tumor imaging. There was no apparent radioactivity in the inflammatory tissue, which can well distinguish benign and malignant disease with 18F-FDG. 18F-FDG and 18F-FLT are no tumor specific tracer, 99mTc-AMD3100, as tumor receptor tracer, has an advantage on distinguishing benign disease from malignant disease.
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