Evaluation of [18F]FDG/[18F]FLT/[18F]FMISO-based micro-positron emission tomography in detection of liver metastasis in human colorectal cancer.

INTRODUCTION: Positron emission tomography (PET) is extensively used in clinical oncology for tumor detection. This study aimed to explore the application of the radiotracers [18F]fluorodeoxyglucose ([18F]FDG), 3'-deoxy-3'- [18F]fluorothymidine ([18F]FLT), and [18F]fluoromisonidazole ([18F]FMISO) in the diagnosis and monitoring of hepatic metastasis in human colorectal cancer (CRC). METHODS: A mouse model of human CRC with hepatic metastasis was established by intrasplenic implantation of human CRC cell lines LoVo or HCT8. Metastatic potential of these two cell lines was evaluated by wound healing assay in vitro and survival analysis. Uptake of radiotracers between LoVo and HCT8 cells and uptake of radiotracers in the resulting mouse tumor models were examined by in vivo and in vitro experiments. Uptake of each radiotracer in hepatic metastatic lesions was quantified and expressed as standard uptake value (SUV). Protein expression of multiple tumor biomarkers was determined in metastatic lesions. The correlation between tracer uptake and tumor marker expression was evaluated using linear regression. RESULTS: LoVo cells exhibited a stronger metastatic potential and a higher radiotracer uptake ability than HCT8 cells, as evidenced by significantly greater wound closure percentage, shorter survival, higher incidence of liver metastases, and higher cellular radiotracer levels in LoVo cells or LoVo cell-xenografted mice. SUV values of [18F]FLT and [18F]FMISO, but not [18F]FDG, in LoVo cell-derived metastatic lesions were significantly greater than those in HCT8 lesions. Mechanistically, the expression of MACC1, HIF-1α, and GLUT-1(metastasis associated in colon cancer 1, MACC1; hypoxia-inducible factor 1-alpha, HIF-1α; and glucose transporter 1, GLUT-1, respectively) in LoVo cell-derived metastatic lesions was more effectively induced than in HCT8-derived ones. A linear regression analysis demonstrated significant positive correlations between [18F]FLT/[18F]FMISO uptake and tumor biomarker expression in metastatic tissues. CONCLUSIONS: [18F]FLT and [18F]FMISO-based PET imaging may serve as a promising method for early detection and monitoring of hepatic metastasis in patients with CRC.

Using receiver operating characteristic curves to evaluate the diagnostic value of the combination of multislice spiral CT and alpha-fetoprotein levels for small hepatocellular carcinoma in cirrhotic patients.

BACKGROUND: The various combination of multiphase enhancement multislice spiral CT (MSCT) makes the diagnosis of a small hepatocellular carcinoma (sHCC) on the background of liver cirrhosis possible. This study was to explore whether the combination of MSCT enhancement scan and alpha-fetoprotein (AFP) level could increase the diagnostic efficiency for sHCC. METHODS: This study included 35 sHCC patients and 52 cirrhotic patients without image evidence of HCC as a control group. The diagnoses were made by three radiologists employing a 5-point rating scale, with postoperative pathologic results as the gold standard. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of the three MSCT combination modes (arterial phase+portal-venous phase, arterial phase+delayed phase, arterial phase+portal-venous phase+delayed phase) and AFP levels for sHCC on the background of liver cirrhosis. RESULTS: The area under ROC curve (AUC), sensitivity, and specificity of the combination of arterial phase+portal-venous phase+delayed phase were 0.93, 93%, and 82%, respectively. The average AUC of the arterial phase+portal-venous phase+delayed phase combination was significantly greater than that of the arterial phase+portal-venous phase (AUC=0.84, P=0.01) and arterial phase+delayed phase (AUC=0.85, P=0.03). Arterial phase+portal-venous phase had a smaller AUC (0.84) than arterial phase+delayed phase (0.85), but the difference was insignificant (P=0.15). After combining MSCT enhancement scan with AFP, the AUC, sensitivity, and specificity were 0.95, 94%, and 83%, respectively, indicating a greatly increased diagnostic efficiency for sHCC. CONCLUSIONS: The combination of AFP and 3 phases MSCT enhancement scan could increase the diagnostic efficiency for sHCC on the background of liver cirrhosis. The application of ROC curve analysis has provided a new method and reference in HCC diagnosis.

Detection and differentiation of early hepatocellular carcinoma from cirrhosis using CT perfusion in a rat liver model.

BACKGROUND: Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in hepatocellular carcinoma (HCC). Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investigate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic (ROC) curves. METHODS: Male Wistar rats were randomly divided into control (n=20) and experimental (n=70) groups. Diethylnitrosamine (DEN) was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion (HPP), hepatic arterial fraction (HAF), hepatic arterial perfusion (HAP), hepatic blood volume (HBV), hepatic blood flow (HBF), mean transit time (MTT) and permeability of capillary vessel surface (PS) data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats (control, pre-carcinoma and early HCC groups) using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan. RESULTS: For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups (P<0.05). HAF had the highest areas under the ROC curves: 0.80 (control vs pre-carcinoma groups) and 0.95 (control vs early HCC groups) with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 (control vs pre-carcinoma groups) and 0.92 (control vs early HCC groups) with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS: CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.

The drug target genes show higher evolutionary conservation than non-target genes.

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

A correlation of computed tomography perfusion and histopathology in tumor edges of hepatocellular carcinoma.

BACKGROUND: The peripheral morphologic characteristics of hepatocellular carcinoma (HCC) reflect tumor growth patterns. Computed tomography (CT) perfusion is a new method to analyze hemodynamic changes in tissues. We assessed the relationship between CT perfusion and histopathologic findings in the periphery of HCC lesions. METHODS: Non-contrast CT, enhanced dual-phase CT, and CT perfusion were performed on 77 subjects (47 patients and 30 controls). Based on the imaging findings of enhanced dual-phase CT, the tumor edges were classified into three types: type I (sharp); type II (blurry); and type III (mixed). The CT perfusion parameters included hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. The tissue sections from resected specimens were subjected to routine hematoxylin and eosin staining and immunohistochemical staining for CD34. The correlations between microvessel density (MVD) and the CT perfusion parameters were analyzed using Pearson's product-moment correlation coefficient. Changes in the perfusion parameters in tumor edges of different tumor types were evaluated. RESULTS: Type I (sharp): the pathologic findings showed fibrous connective tissue capsules in the tumor edges, and an MVD ≤30/mm2. Type II (blurry): the histology showed that the edges were clear with no capsules and an MVD>30/mm2. Type III (mixed): the pathology was similar to that of types I and II, and an MVD>30/mm2. Hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion were significantly increased in the tumor edges of HCC patients compared to those of the controls (P<0.05). The correlation between CT perfusion parameters and MVD was higher in blurry tumor edges of type II than in those of types I or III. CONCLUSION: CT perfusion imaging of tumor edges may be helpful in revealing histopathological features, and indirectly reflect angiogenic changes of HCCs.

CT assessment of liver hemodynamics in patients with hepatocellular carcinoma after argon-helium cryoablation.

BACKGROUND: Assessment of tumor response after argon-helium cryoablation is critical in guiding future therapy for unresectable hepatocellular carcinoma. This study aimed to evaluate liver hemodynamics in hepatocellular carcinoma after argon-helium cryoablation with computed tomography perfusion. METHODS: The control group comprised 40 volunteers without liver disease. The experimental group was composed of 15 patients with hepatocellular carcinoma treated with argon-helium cryoablation. Computed tomography perfusion parameters were measured: hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. RESULTS: After treatment, in the tumor foci, permeability of capillary vessel surface was higher, and hepatic blood flow, hepatic blood volume, hepatic arterial fraction, and hepatic arterial perfusion values were lower (P<0.05). In the liver parenchyma surrounding the tumor, hepatic arterial perfusion was significantly lower (P<0.05); however, there was no significant difference in hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial fraction, or hepatic portal perfusion (P>0.05). CONCLUSION: Computed tomography perfusion can evaluate tumor response after argon-helium cryoablation.