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Open Access 01-08-2015 | Original Article
Evaluation of the therapeutic efficacy of a MEK inhibitor (TAK-733) using 18F-fluorodeoxyglucose-positron emission tomography in the human lung xenograft model A549
Published in: Annals of Nuclear Medicine | Issue 7/2015
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Objective
The aim of this study was to evaluate the potential of 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) for monitoring the therapeutic efficacy of TAK-733, an inhibitor of mitogen-activated protein kinase kinase, in nude rats bearing A549 (human lung carcinoma) xenografts.
Methods
TAK-733 was administered orally by gavage to nude xenograft rats for 2 weeks, at dosage levels of 0 (0.5 % w/v methylcellulose solution), 1, 3, and 10 mg/kg/day (n = 8/dose). Tumor size was measured before treatment (day 0), and on days 1, 3, 7, 9, 11, and 14. PET scans were performed pretreatment (day 0), and on days 2, 4, 7, 10, and 14. Tracer accumulations in tumor tissue were quantified as the mean standard uptake value (SUVmean).
Results
No deaths or treatment-related body weight losses occurred during the study period. TAK-733 showed dose-dependent inhibition of tumor growth and 18F-FDG uptake in tumor tissue. At a dosage of 10 mg/kg, TAK-733 treatment produced a statistically significant reduction in tumor weight from day 11 compared with the vehicle group (P < 0.05). Tumor growth was inhibited in the 10 mg/kg group with a treated/control value of 31 % on day 14. The SUVmean on day 2 in this dosage group was statistically lower than that observed on day 0, and that seen in the vehicle group on day 2 (P < 0.05 for both comparisons). Furthermore, this reduction in SUVmean at 10 mg/kg was maintained over time. In the two lower dosage groups (1 and 3 mg/kg), SUVmean gradually increased over time.
Conclusions
18F-FDG-PET enabled early determination of late anti-tumor activity in response to TAK-733 treatment.