Dose-response relationship in cyclophosphamide-treated B-cell lymphoma xenografts monitored with [18F]FDG PET

Eur J Nucl Med Mol Imaging. 2010 Aug;37(9):1688-95. doi: 10.1007/s00259-010-1479-0. Epub 2010 May 12.

Abstract

Purpose: Although [(18)F]FDG PET can measure therapy response sooner and more accurately than morphological imaging techniques, there is still some debate as to whether [(18)F]FDG uptake really reflects changes in the viable cell fraction. In this study changes in [(18)F]FDG uptake were investigated in a lymphoma model at several time-points after treatment and with different doses of chemotherapy. Data were analysed in terms of several parameters.

Methods: SCID mice were subcutaneously inoculated with 5x10(6) Daudi cells in the right thigh. One group was not treated (control group). The other groups received cyclophosphamide 75 mg/kg (low-dose group), 125 mg/kg (medium-dose group) and 175 mg/kg (high-dose group) on day 0. Sequential [(18)F]FDG small-animal PET (microPET) scans were performed on days 0, 2, 6, 9, 13 and 16 after treatment. The mean and maximum standardized uptake value (SUV(mean) and SUV(max)), metabolic tumour volume (Vol(metab)) and total lesion glycolysis (TLG) were calculated.

Results: A significant decrease in [(18)F]FDG uptake was observed on day 2 in the medium-dose and high-dose groups and on day 6 in the low-dose group, all preceding morphological changes. SUV(mean) and SUV(max) formed a plateau from day 6 to day 9, corresponding to the known influx of inflammatory cells. No obvious plateau was observed with TLG which was found to be the most sensitive parameter clearly differentiating the low-dose group from the medium- and high-dose groups early after therapy.

Conclusion: [(18)F]FDG uptake was able to reflect the dose-response relationship for cyclophosphamide. TLG was the best parameter for dose-related response assessment in this tumour model.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cyclophosphamide / pharmacology*
  • Cyclophosphamide / therapeutic use
  • Dose-Response Relationship, Drug
  • Fluorodeoxyglucose F18*
  • Humans
  • Lymphoma, B-Cell / diagnostic imaging*
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, B-Cell / pathology
  • Mice
  • Positron-Emission Tomography*
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays / methods*

Substances

  • Fluorodeoxyglucose F18
  • Cyclophosphamide