| Objective: To investigate the killing effect of 5 -[(125)~I] iodo-2'-deoxyuridine ((125)~I-UdR)on A549 lung cancer cell lines and the factors of influencing effect in vitro , research therapeutic effect on Lewis lung cancer, biodistribution and safety of (125)~I-UdR in C57 tumour-bearing mice, and evaluate the value of treating lung cancer . Methods: (1)(125)~I-UdR was synthesized by nitric acid oxidation method. (2) The amounts of (125)~I-UdR taken by the cells and caryons were measured through counting the radioactivity after incubating for 48 hour in RPMI-1640 culturing medium containing different concentration of (125)~I-UdR and in 100kBq/ml dosage of (125)~I-UdR after incubating different time. The killing effect of (125)~I-UdR on A549 cell was evaluated by colony forming method.(3)The model of C57 tumour-bearing mice was developed by inoculation of Lewis lung cell. The biodistribution of (125)~I-UdR in mice was estimated by SPECT scintigraphy and the radioactivities in various tissues were determined by γ-counter after intratumoural injection of (125)~I-UdR . The shapes and pathological changes of tumour were observed and the pharmic safety was evaluated by observing marrow cell and measuring blood index ,live function and kidney function. Finally, the surviving time of tumour-bearing mice was traced after (125)~I-UdR injection. Results: (1)The amounts of (125)~I-UdR taken by the cells and karyons increased with the rate of dose of (125)~I-UdR in the medium among 0.1-500kBq/ml, correlation coefficient r=0.97 and r=0.98, respectively. Meanwhile , the concentration that they ingested (125)~I-UdR was time-dependent among 2-48 hour, correlation coefficient r=0.88 and r=0.71 , respectively. The amounts of radioactivity ingestion were significantly higher in 125I-UdR group than that in Na125I group in different concentration culturing medium, p<0.01 except for p<0.05 in 0.1kBq/ml concentration. Likewise , the radioactivity concentration ingested by cells in 125I-UdR group was markedly highter than that in Na125I group in different incubation time,p<0.01. Furthermore,the radioactivity concentration of 125I-UdR uptake in A549 cell was evidently highter than that in ECV304 cell in different incubation time, p<0.01 except for p<0.05 in 2 hour. The surviving fraction was gradually decreased with increasing of 125I-UdR concentration in culturing medium. (2)After injecting 125I-UdR into tumour , 125I-UdR was persistedly incorporated in tumour tissue and resulted in tumour tissue serious necrosis .In 48 hour after injection,the tumour-to-normal tissue ratio ( T/NT ) of radioactivity is 86 -273 times while no significant side effects on blood index ,marrow cell, liver function ,kidney function and other normal tissue were found. Conclusion: (1)125I-UdR could be ingested by A549 cells in culturing medium,which showed strong killing effects on the cells. Moreover, the concentration of 125I-UdR ingestion was influenced by the dose in the medium and culturing time. (2)125I-UdR retained within tumour tissue for a long time,caused tumour tissue serious necrosis and did not find evident side effects on normal tissue after intratumoural injection of 125I-UdR. The survival time of tumour-bearing mice was markedly prolonged in 125I-UdR therapy group. In a word,125I-UdR intratumour radiotherapy through direct injection into tumour is an efficient and safe method in treatment of lung cancer.
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