Impact of Angiogenesis-Related Gene Expression on the Tracer Kinetics of¹⁸F-FDG in Colorectal Tumors

Abstract

18 F-FDG kinetics are primarily dependent on the expression of genes associated with glucose transporters and hexokinases but may be modulated by other genes. The dependency of 18 F-FDG kinetics on angiogenesis-related gene expression was evaluated in this study. Methods: Patients with primary colorectal tumors (n 5 25) were examined with PET and 18 F-FDG within 2 days before surgery. Tissue specimens were obtained from the tumor and the normal colon during surgery, and gene expression was assessed using gene arrays. Results: Overall, 23 angiogenesis-related genes were identified with a tumor-to-normal ratio exceeding 1.50. Analysis revealed a significant correlation between k1 and vascular endothelial growth factor (VEGF-A, r 5 0.51) and between fractal dimension and angiopoietin-2 (r 5 0.48). k3 was negatively correlated with VEGF-B (r 5 20.46), and a positive correlation was noted for angiopoietin-like 4 gene (r 5 0.42). A multiple linear regression analysis was used for the PET parameters to predict the gene expression, and a correlation coefficient of r 5 0.75 was obtained for VEGF-A and of r 5 0.76 for the angiopoietin-2 expression. Thus, on the basis of these multiple correlation coefficients, angiogenesis-related gene expression contributes to about 50% of the variance of the 18 F-FDG kinetic data. The global 18 F-FDG uptake, as measured by the standardized uptake value and influx, was not significantly correlated with angiogenesisassociated genes. Conclusion: 18 F-FDG kinetics are modulated by angiogenesis-related genes. The transport rate for 18 F-FDG (k1) is higher in tumors with a higher expression of VEGF-A and angiopoietin-2. The regression functions for the PET parameters provide the possibility to predict the gene expression of VEGF-A and angiopoietin-2.

18F‑fluorodeoxyglucose positron emission tomography̸computed tomography for the prediction of survival in patients with advanced esophageal cancer who have undergone neoadjuvant chemotherapy

“…Several investigators have recently reported that the size of the metastatic lymph node is one of the strongest prognostic factors in esophageal cancer (27)(28)(29). Moreover, higher SUV max values indicate a higher malignant potential of cancer cells through a variety of mechanisms, such as cell proliferation, tissue hypoxia and angiogenesis (30)(31)(32)(33).…”

Reply: Comment on: “Tumor Aggressiveness and Patient Outcome in Cancer of the Pancreas Assessed by Dynamic 18F-FDG PET/CT”

“…Furthermore, the use of kinetic parameters may help to differentiate between benign and less aggressive tumors (e.g., lipomas from low-grade liposarcomas) (6). In a recent paper, we demonstrated a correlation between k 1 and angiogenesis-related genes (7). Based on dynamic datasets, parametric imaging can be applied using different algorithms.…”

Advanced kinetic modelling strategies: towards adoption in clinical PET imaging

“…In lung cancer, dynamic 18 F-FDG imaging followed by kinetic analysis has been shown to assist in differentiation between squamous cell carcinoma and adenocarcinoma, revealing differences in kinetics between these subtypes [8]. In colorectal tumours, kinetic analysis may help to differentiate between primary tumours and normal tissue [9], and kinetic parameters may provide information on proliferation and angiogenesis [10,11]. The literature contains a multitude of studies highlighting the potential significance of kinetic modelling in clinical oncology and drug development, as several critical reviews have shown [12][13][14].…”