Impact of angiogenesis-related gene expression on the tracer kinetics of 18F-FDG in colorectal tumors.
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.


CONCLUSIONS
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.
Strauss
Ludwig G
LG
Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany. lgs@ads-lgs.de
Koczan
Dirk
D
Klippel
Sven
S
Pan
Leyun
L
Cheng
Caixia
C
Willis
Stefan
S
Haberkorn
Uwe
U
Dimitrakopoulou-Strauss
Antonia
A
D042702:Angiopoietin-2 / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D020869:Gene Expression Profiling; D006801:Humans; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D042702:Angiopoietin-2; D019275:Radiopharmaceuticals; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019788:Fluorodeoxyglucose F18