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

J Nucl Med. 2008 Aug;49(8):1238-44. doi: 10.2967/jnumed.108.051599. Epub 2008 Jul 16.

Abstract

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.

MeSH terms

  • Angiopoietin-2 / biosynthesis
  • Colorectal Neoplasms / blood supply*
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / metabolism
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Gene Expression Profiling
  • Humans
  • Neovascularization, Pathologic / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Positron-Emission Tomography
  • Radiopharmaceuticals / pharmacokinetics*
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • Angiopoietin-2
  • Radiopharmaceuticals
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fluorodeoxyglucose F18