Prediction of metastatic tendency of human colorectal cancer using PET imaging in nude mice / 中华核医学杂志

ABSTRACT

Objective To evaluate the predictive value of 18F-fluorodeoxyglucose (FDG) and 18F-fluorothymidine(FLT) PET in monitoring the metastatic potential of human colorectal cancer (CRC).Methods Human CRC cell lines SW480 and SW620 were cultured and implanted into nude mice to create CRC models. Tumor growth,metastatic status and survival were assessed in CRC bearing mice. Uptake of 18F-FDG and 18F-FLT in SW480 and SW620 cells was detected In vitro at 0,30,60,90,120 min after incubation. PET images of both tracers were acquired for SW480 and SW620 tumor-bearing mice using the small animal PET at 60 min after tracer injection. Region of interest (ROI) was drawn using Image J software on reconstructed PET images. Immunocytochemistry and Western blot analysis of the tumor tissue were performed. The correlation between tracer uptake and tumor marker expression was evaluated using linear regression. Results Compared with SW620 tumor-bearing mice,SW480 induced tumor grew much faster ( t = - 3.332,P = 0.004),the tumor-bearing mice had more serious dyscrasia ( t = 2.240,P = 0.038 ),shorter survival and higher metastatic rate. In vitro study,the uptake of both 18F-FDG and 18F-FLT in SW620 cells was lower than that in SW480 cells. 18F-FLT uptake was higher than 18F-FDG uptake in both SW480 and SW620 cells. After incubation for 60 min,the uptake of 18F-FDG in SW480 and SW620 cells was ( 1.76 ± 0.87 )% and ( 1.14 ± 0.38 )%,respectively ( t = - 2.507,P = 0.021 ); while the uptake of 18F-FLT in SW480 and SW620 cells was (5.21 ± 1.60)% and (2.90 ± 1.82)%,respectively (t =3.497,P =0.002). In micro-PET study,the 18F-FDG radioactivity ratio of tumor to non-tumor (T/NT) in SW480 and SW620 tumors was 2.69 ± 0.98 and 3.09 ± 1.26 respectively (t =0.657,P =0.524); while T/NT of 18F-FLT in SW480 and SW620 tumors was 3.65 ±0.51 and 2.22 ±0.42 (t =6.491,P ＜0.001 ),respectively. In immunocytochemistry and western blot assay,heat shock protein(HSP) 27,Integrin β3,vascular endothelial growth factor receptor 2 ( VEGFR2 ) and Ki67 were all over expressed in two kinds of tumor cells with different intensities. HSP27 and Integrin β3 expression was higher in SW480 cells than that in SW620 cells. While VEGFR and Ki67 expression was lower in SW480 cells than that in SW620 cells. The uptake of 18F-FLT closely correlated with the expression of HSP27 ( r =0.924,P =0.004) and Integrin β3 (r=0.813,P =0.025). 18F-FDG uptake inversely correlated with the survival of tumor-bearing mice (r =0.500,P=0.017). Conclusions The uptake of 18F-FDGand 18F-FLT may reflect different biological characteritics of CRC. High 18F-FLT uptake in CRC on PET scan may predict high metastatic tendency.