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
Purpose: To generate parametric images of tumor hypoxia in a tumor-bearing rat model using voxel-based compartmental analysis of dynamic fluorine-18 labeled misonidazole (18F-FMISO) microPET? images, and to compare th...Purpose: To generate parametric images of tumor hypoxia in a tumor-bearing rat model using voxel-based compartmental analysis of dynamic fluorine-18 labeled misonidazole (18F-FMISO) microPET? images, and to compare the parametric images thus derived with static “late” 18F-FMISO microPET? images for the detection of tumor hypoxia. Materials and Methods: Nude rats bearing HT-29 colorectal carcinoma xenografts (≈1.5 - 2 cm in diameter) in the right hind limb were positioned in a custom-fabricated, animal-specific foam mold. Animals were injected via the tail vein with ≈55.5 MBq 18F-FMISO and continuously imaged for either 60 or 120 minutes, with additional late static images up to 3 hour post-injection. The raw list-mode data was reconstructed into 37 - 64 frames with earlier frames of shorter time durations (12 - 15 seconds) and later frames of longer durations (up to 300 seconds). Time activity curves (TACs) were generated over regions encompassing the tumor as well as an artery, the latter for use as an input function. A beta version of a compartmental modeling package (BioGuide?, Philips Healthcare) was used to generate parametric images of k3 and Ki, rate constants of entrapment and flux of 18F-FMISO, respectively. Results: Data for 7 HT-29 tumor xenografts were presented, 6 of which yielded clear areas of tumor hypoxia as defined by Ki/k3 maps. Importantly, intratumoral foci with high 18F-FMISO uptakes on the late images did not always exhibit high Ki/k3 values and may there- fore represent false-positives for radiobiologically significant hypoxia. Conclusions: This study attempts to quantify tumor hypoxia using compartmental analysis of dynamic 18F-FMISO PET images in rodent xenograft tumor models. The results demonstrate feasibility of the approach in small-animal imaging studies, and provide evidence for the possible unreliability of late-time static imaging of 18F-FMISO PET in identifying tumor hypoxia.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.
文摘Purpose: To generate parametric images of tumor hypoxia in a tumor-bearing rat model using voxel-based compartmental analysis of dynamic fluorine-18 labeled misonidazole (18F-FMISO) microPET? images, and to compare the parametric images thus derived with static “late” 18F-FMISO microPET? images for the detection of tumor hypoxia. Materials and Methods: Nude rats bearing HT-29 colorectal carcinoma xenografts (≈1.5 - 2 cm in diameter) in the right hind limb were positioned in a custom-fabricated, animal-specific foam mold. Animals were injected via the tail vein with ≈55.5 MBq 18F-FMISO and continuously imaged for either 60 or 120 minutes, with additional late static images up to 3 hour post-injection. The raw list-mode data was reconstructed into 37 - 64 frames with earlier frames of shorter time durations (12 - 15 seconds) and later frames of longer durations (up to 300 seconds). Time activity curves (TACs) were generated over regions encompassing the tumor as well as an artery, the latter for use as an input function. A beta version of a compartmental modeling package (BioGuide?, Philips Healthcare) was used to generate parametric images of k3 and Ki, rate constants of entrapment and flux of 18F-FMISO, respectively. Results: Data for 7 HT-29 tumor xenografts were presented, 6 of which yielded clear areas of tumor hypoxia as defined by Ki/k3 maps. Importantly, intratumoral foci with high 18F-FMISO uptakes on the late images did not always exhibit high Ki/k3 values and may there- fore represent false-positives for radiobiologically significant hypoxia. Conclusions: This study attempts to quantify tumor hypoxia using compartmental analysis of dynamic 18F-FMISO PET images in rodent xenograft tumor models. The results demonstrate feasibility of the approach in small-animal imaging studies, and provide evidence for the possible unreliability of late-time static imaging of 18F-FMISO PET in identifying tumor hypoxia.
