18F-FDG kinetics and gene expression in giant cell tumors

J Nucl Med. 2004 Sep;45(9):1528-35.

Abstract

18F-FDG kinetics were evaluated by use of compartment and noncompartment models of giant cell tumors. The kinetic data were compared with the gene expression data for a subgroup of patients.

Methods: Nineteen patients with giant cell tumors were examined with PET and 18F-FDG, and tracer kinetics were assessed quantitatively. A 2-compartment model, including the transport constants k1-k4 as well as the vascular fraction (VB) for 18F-FDG, was used for evaluation of the data. A noncompartment model was used to calculate the fractal dimension of the 18F-FDG time-activity curve to assess the heterogeneity of the tracer kinetics. Furthermore, tumor specimens obtained from 5 patients were assessed with gene chip technology (U95A), and these data were compared with the quantitative 18F-FDG data.

Results: The giant cell tumors showed generally enhanced 18F-FDG uptake 1 h after tracer application, with a mean 18F-FDG standardized uptake value (SUV) of 4.8 (range, 1.8-9.4). Quantitative evaluation of tracer kinetics showed a preferential increase for 18F-FDG transport, with a mean k1 of 0.340. The vascular fraction accounted for 35% of the tumor volume and was high compared with those for other tumors, such as soft-tissue sarcomas. 18F-FDG kinetics were heterogeneous, with a fractal dimension of 1.3. Gene chip analysis showed that the expression of 137 genes (1.1%) exceeded the median expression value of the reference gene, beta2-microglobulin. The highest expression was observed for the gene for the small, leucine-rich proteoglycan I (biglycan), which is important for bone cell differentiation and proliferative activity. Correlation analysis revealed an association of 18F-FDG data with the expression of several genes. Mainly genes related to angiogenesis were associated with the compartment parameters. The SUV at 56-60 min was correlated with the expression of vascular endothelial growth factor A (angiogenesis) and cell division cycle 2 protein (proliferation).

Conclusion: Despite their classification as benign tumors, giant cell tumors have generally enhanced 18F-FDG uptake, mainly attributable to an enhanced vascular fraction and increased 18F-FDG transport. A comparison of gene chip data and 18F-FDG kinetic data showed a close association of quantitative 18F-FDG results and the expression of genes related to angiogenesis.

Publication types

  • Clinical Trial
  • Comparative Study
  • Validation Study

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Fluorodeoxyglucose F18 / pharmacokinetics*
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic*
  • Giant Cell Tumors / diagnostic imaging*
  • Giant Cell Tumors / genetics
  • Giant Cell Tumors / metabolism*
  • Humans
  • Kinetics
  • Metabolic Clearance Rate
  • Neoplasm Proteins / metabolism*
  • Oligonucleotide Array Sequence Analysis / methods
  • Radiopharmaceuticals / pharmacokinetics
  • Statistics as Topic
  • Tomography, Emission-Computed

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18