Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of t...Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value(SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer(CRC) in mice. Methods: Colorectal liver metastases(CRLM) xenograft models were established by injecting tumor cells(LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. ^(18)F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^(18)F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the ^(18)F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1 α(HIF-1 α) and serum starvation-induced glucose transporter 1(GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, ^(18)F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between ^(18)F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ^(18)F-FMISO SUVmax ratio and HIF-1 α or GLUT-1 expression in tumor-bearing tissues. Conclusions: ^(18)F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.展开更多
Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with c...Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.展开更多
基金supported by grants from the National Natural Science Foundation of China(81471736,81671760 and 81873910)Scientific Research Transformation Special Fund of Heilongjiang Academy of Medical Sciences(2018415)Scientific Research Project of Health and Family Planning Commission of Heilongjiang Province(CR201807)
文摘Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value(SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer(CRC) in mice. Methods: Colorectal liver metastases(CRLM) xenograft models were established by injecting tumor cells(LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. ^(18)F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^(18)F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the ^(18)F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1 α(HIF-1 α) and serum starvation-induced glucose transporter 1(GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, ^(18)F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between ^(18)F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ^(18)F-FMISO SUVmax ratio and HIF-1 α or GLUT-1 expression in tumor-bearing tissues. Conclusions: ^(18)F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.
基金supported by grants from the National Natural Science Foundation of China(81471736 and 81671760)the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(2015BAI01B09)Project of Research Foundation of the Talent of Scientific and Technical Innovation of Harbin City(2016RAXYJ063)
文摘Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.