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Impact of Angiogenesis-Related Gene Expression on the Tracer Kinetics of ¹⁸F-FDG in Colorectal Tumors

¹ Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany; ² Institute of Immunology, University Rostock, Rostock, Germany; ³ Surgical Clinic A, Klinikum Ludwigshafen, Ludwigshafen, Germany; and ⁴ Division of Nuclear Medicine, Ruprecht-Karls-University, Heidelberg, Germany

Correspondence: For correspondence or reprints contact: Ludwig G. Strauss, Medical PET Group—Biological Imaging (E060-1), Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. E-mail: lgs{at}ads-lgs.de

¹⁸F-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 ¹⁸F-FDG kinetics on angiogenesis-related gene expression was evaluated in this study. Methods: Patients with primary colorectal tumors (n = 25) were examined with PET and ¹⁸F-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 = 0.51) and between fractal dimension and angiopoietin-2 (r = 0.48). k3 was negatively correlated with VEGF-B (r = –0.46), and a positive correlation was noted for angiopoietin-like 4 gene (r = 0.42). A multiple linear regression analysis was used for the PET parameters to predict the gene expression, and a correlation coefficient of r = 0.75 was obtained for VEGF-A and of r = 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 ¹⁸F-FDG kinetic data. The global ¹⁸F-FDG uptake, as measured by the standardized uptake value and influx, was not significantly correlated with angiogenesis-associated genes. Conclusion: ¹⁸F-FDG kinetics are modulated by angiogenesis-related genes. The transport rate for ¹⁸F-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.

Key Words: PET • ¹⁸F-FDG • angiogenesis • gene expression • gene array

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