Biodistribution and anti-cancer potential of ~(131)I-17-AAG in NSCLC xenograft-bearing nude mice

OBJECTIVE:To study the biodistribution and therapeutic efficiency of 131I-17-AAG in human non-small cell lung cancer(NSCLC) xenografts in mice.METHODS:In vivo imaging was performed through 131I-17-AAG intratumoral injection or tail veil injection,Na131I intratumoral injection and the blocking imaging group,using 12 xenografts with dosage of 5.55 MBq in 0.1 mL solution per mouse.The mice were sacrificed and tumor tissues were separated.Examinations were done through electron microscopy for tumor cell apoptosis observation and through immunohistochemistry assay for Bcl-2 and Ki-67 expression,compared with blank control (n=3).Another 24 xenografts through 131I-17-AAG intratumoral or intravenous delivery (1.85 MBq in 0.1 mL solution per mouse) were sacrificed at different time points.The blood and major organs were obtained for radioactivity measurement.RESULTS:In vivo imaging indicated tumor retention by 131I-17-AAG intratumoral injection persisted for a long time,evidenced by the results of biodistribution study.While tumor uptake in tail veil injection group was not obvious but with a rapid systemic clearance,and Na131I control group had a rapid radioactivity clearance without tumor retention.In the blocking group,tumor uptake decreased significantly compared with the unblocked group.131I-17-AAG injection groups had more tumor inhibition efficacy observed by electron microscopy and lower Bcl-2 and Ki67 expression than control groups.There were statistical significance among 131I-17-AAG groups and control groups (Pmax=0.004).CONCLUSION:131I-17-AAG through intratumoral injection has certain pharmacodynamic distribution and effects on tumor tissues and may have great potential for tumor therapy.