Early effects of FOLFOX treatment of colorectal tumour in an animal model: assessment of changes in gene expression and FDG kinetics

  • Ludwig G. Strauss
  • Johannes Hoffend
  • Dirk Koczan
  • Leyun Pan
  • Uwe Haberkorn
  • Antonia Dimitrakopoulou-Strauss
Original Article

DOI: 10.1007/s00259-009-1102-4

Cite this article as:
Strauss, L.G., Hoffend, J., Koczan, D. et al. Eur J Nucl Med Mol Imaging (2009) 36: 1226. doi:10.1007/s00259-009-1102-4
  • 299 Downloads

Abstract

Purpose

The very early chemotherapeutic effects of the FOLFOX (fluorouracil, folinic acid, oxaliplatin) protocol were assessed in mice implanted with a human colorectal cell line. The aim of this study was to identify changes in gene expression patterns and to detect combinations of PET parameters that may be helpful in identifying treated tumours early after chemotherapy using dynamic PET studies.

Methods

A human colorectal cell line (HCT 116) was used in nude mice. Dynamic PET studies were performed in untreated (n = 13) and treated (n = 12) animals. The data were assessed using compartmental and noncompartmental analysis. The removed tumour specimens were assessed by gene array analysis to obtain quantitative information on gene expression.

Results

One chemotherapeutic treatment using the FOLFOX protocol resulted in an upregulation of 2,078 gene probes by more than 25%, while 2,254 probes were downregulated following treatment. The gene array data demonstrated primarily an enhancement of genes related to apoptosis. In particular, the apoptosis antigen 1 (APO-1), p21 and the G protein-coupled receptor 87 (G-87) were 2.6- to 3.3-fold upregulated as compared to the expression in untreated animals. There was a 100% separation of untreated and treated animals on the basis of these three genes. The SUV and the FDG kinetic parameters obtained by compartmental and noncompartmental fitting were not significantly different when individual parameters were compared between groups. However, classification analysis of the combination of the PET parameters VB, K1, k3, and influx revealed an overall accuracy of 84%. We were able to identify 91.7% (11/12) of the treated animals and 76.9% (10/13) of the untreated animals correctly using the classification analysis of PET data.

Conclusion

Even one chemotherapeutic treatment using FOLFOX has an impact on gene expression and significantly modulates FDG kinetics. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data are promising tools to identify those tumours that demonstrate a chemotherapeutic effect very early following treatment.

Keywords

PET FDG Colorectal Chemotherapy Gene expression 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ludwig G. Strauss
    • 1
    • 5
  • Johannes Hoffend
    • 2
  • Dirk Koczan
    • 3
  • Leyun Pan
    • 1
  • Uwe Haberkorn
    • 1
    • 4
  • Antonia Dimitrakopoulou-Strauss
    • 1
  1. 1.Clinical Cooperation Unit Nuclear MedicineGerman Cancer Research CenterHeidelbergGermany
  2. 2.Institute of Diagnostic and Interventional RadiologyKlinikum LudwigshafenLudwigshafenGermany
  3. 3.Institute of ImmunologyUniversity of RostockRostockGermany
  4. 4.Department of Nuclear MedicineUniversity of HeidelbergHeidelbergGermany
  5. 5.Medical PET Group - Biological Imaging, Clinical Cooperation Unit Nuclear MedicineGerman Cancer Research CenterHeidelbergGermany

Personalised recommendations