18F-Fluorothymidine (FLT) as tumor response predictor for anti-epidermal growth factor receptor (EGFR) antibody in human lung cancer xenograft

Abstract

e22088 Background: Specific EGFR inhibition therapies are currently promising and advanced in the clinical setting. It is revealed patients with a colorectal cancer bearing mutated K-ras do not benefit from cetuximab, a chimeric mouse-human antibody to EGFR. However, appropriate evaluation of the therapeutic effects has not been clarified yet, because of the lack of reliable tumor response predictors. Measurement of tumor proliferative activity by PET using FLT may serve to assess early response of the therapy. The purpose of this study is to determine whether 18F- FLT is useful to evaluate very early response to cetuximab treatment in human lung cancer cell line xenograft. Methods: Human tumor xenograft model was established in male BALB/c athymic mice by human lung cancer cell line NCI-H1975, which expresses L858R/T790M-EGFR. These mice were assigned to two groups (n=5, each group): control and cetuximab-treated groups. Cetuximab was intra-peritoneally given 1.0mg/body once on the first day. Biodistribution of 3H-FLT (%Inject Dose/g/kg) were studied two days after the treatment. Immunohistochemical staining of EGFR, phosphorylated EGFR (pEGFR), and nuclear antigen Ki-67 as a tumor cell proliferation marker in tumor tissues were also studied to assess early effects of cetuximab. Results: FLT uptake was high in tumors compared with any other organs. Two days after the cetuximab therapy, the mean value of FLT uptake in tumor was significantly decreased to 55% of control value (0.38 ± 0.03 in control group vs. 0.21 ± 0.07 in cetuximab-treated group; p < 0.05). There were no statistical differences in the tumor volume and body weight of mice between each group. High expression of EGFR and Ki-67 were observed in this xenograft. As compared with control, Ki-67 expression was remarkably decreased in cetuximab-treated group, while there were no definite changes in expression of EGFR and pEGFR. Conclusions: In this animal model, FLT uptake and Ki-67 expression were decreased in cetuximab- treated group just two days after the treatment start. These results indicate FLT-PET can be a useful predictor to evaluate very early response to molecular targeted medicine such as cetuximab before significant change of tumor size. No significant financial relationships to disclose.