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Anti-tumor effect of iodine-131 labeled 17-AAG on H460 human non-small lung cancer bearing nude mice

¹ Nuclear Medicine Technology Inst., Southeast U., Nanjing, Jiangsu, China

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Objectives: 17-allylamino-17-demethoxygeldanamycin (17-AAG)as an Hsp90 inhibitor in clinical trials is directed toward a specific molecular target.The aim is to observe inhibitive effects of iodine-131 labeled 17-AAG on H460 human non-small lung cancer bearing mice.

Methods: 131I labeled17-AAG was achieved with hydrogen peroxide.28 BALB/c nude mice bearing H460 tumor were divided in 7 groups,including tail vein injection and intratumoral injection,with three different radiation doses:5.5MBqx2,11.0MBq and 5.5MBq,and a therapy control group.Another two tumor-bearing mice with intratumoral injection of Na131I solution were set up as an imaging control group.After dynamically observing the growth of tumor for 16d,all of the mice were sacrificed.Tumor tissues were examined by light and electron microscopy and immunohistochemistry assay.

Results: SPECT imaging evidences 131I-17-AAG had a high affinity, being a persistant accumulation in tumor.All therapy groups had antitumor effects.The group of intratumoral injection twice gained the best result with the tumor inhibition ratio of 86.77%±4.57% at 16d. There was no significant difference between 5.5MBqx2 group and 11.0MBq group both via intratumoral injection(P> 0.05),While other groups differed in inhibitive rates(P< 0.05).The morphologic results showed tumor structures were increasingly destroyed as the rising of tumor inhibition.Compared with the control group,in treatment groups HSP90antigen expression in tumor cell declined(P< 0.05).

Conclusions: All groups had certain inhibitive effects,especially in intratumoral injection groups.131I-17-AAG may have great potential as an anti-tumor drug for clinical therapy.

Research Support: Supported by grant 30470500 from National Natural Science Foundation of China.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sun, J. Articles by Lan, X. PubMed Articles by Sun, J. Articles by Lan, X.