Monitoring response to gefitinib in nude mouse tumor xenografts by 18F-FDG microPET-CT: Correlation between 18F-FDG uptake and pathological response

Abstract

Background: The purpose of this study is to investigate whether 18F-fluorodeoxyglucose (FDG) micro-positron emission tomography-computed tomography (microPET-CT) can be used to monitor a metabolic response to gefitinib in nude mouse tumor xenografts. Methods: Sixteen nude mice were implanted with human A431 epidermoid carcinoma cells and ten with human A549 lung adenocarcinoma cells, and the tumors were allowed to grow to an approximate size of 150mm3. Ten and five of these mice, respectively, received intragastric gefitinib (100mg/kg) once daily for 14days, whereas six and five, respectively, received sterile water. Tumor metabolic activity was assessed by 18F-FDG microPET imaging before treatment (day 0) and on days 2, 7, and 14. Tumor uptake of 18F-FDG was determined from a region-of-interest drawn around the tumor, and the maximum percentage injected dose per gram (%ID/gmax) was calculated. Tumor volume measured on day 14 by microCT was used to categorize tumors as sensitive, stable, or resistant to gefitinib, and pathologic changes in these tumors were analyzed. Results: On day 2, the average changes in 18F-FDG uptake by A431 tumors sensitive, stable, and resistant to gefitinib were -30.92%±6.66%, -5.68%±6.95%, and 7.72%±3.85%, respectively (P<0.05 each), with no significant differences in the sizes of tumors sensitive and stable to gefitinib (P=0.169). On day 7, sensitive tumors were significantly smaller than stable tumors (P=0.034). On day 14, areas of necrosis were observed in gefitinib-sensitive tumors, with tumor necrosis ratios differing significantly among the sensitive, stable, and control groups (P<0.05 each). In mice implanted with A549 cells, however, tumor 18F-FDG uptake, volume, and percent necrosis did not differ significantly between gefitinib-treated and untreated mice on days 0, 2, 7, and 14 (P>0.05 each). Conclusions: F-FDG uptake is a sensitive method of detecting metabolic changes in tumors associated with therapy in vivo.