European Journal of Nuclear Medicine and Molecular Imaging

, Volume 36, Issue 4, pp 616–623

Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target

Authors

  • Paolo Farace
    • Department of Morphological-Biomedical Sciences, Section of Anatomy and HistologyUniversity of Verona
  • Daniela D’Ambrosio
    • Department of Nuclear MedicinePoliclinico ‘S. Orsola-Malpighi’
  • Flavia Merigo
    • Department of Morphological-Biomedical Sciences, Section of Anatomy and HistologyUniversity of Verona
  • Mirco Galiè
    • Department of Morphological-Biomedical Sciences, Section of Anatomy and HistologyUniversity of Verona
  • Cristina Nanni
    • Department of Nuclear MedicinePoliclinico ‘S. Orsola-Malpighi’
  • Antonello Spinelli
    • Department of Nuclear MedicinePoliclinico ‘S. Orsola-Malpighi’
  • Stefano Fanti
    • Department of Nuclear MedicinePoliclinico ‘S. Orsola-Malpighi’
  • Anna Degrassi
    • Nerviano Medical Sciences
  • Andrea Sbarbati
    • Department of Morphological-Biomedical Sciences, Section of Anatomy and HistologyUniversity of Verona
    • PET Centre, Department of Nuclear Medicine‘S. Maria della Misericordia’ Hospital
  • Pasquina Marzola
    • Department of Morphological-Biomedical Sciences, Section of Anatomy and HistologyUniversity of Verona
Original Article

DOI: 10.1007/s00259-008-1012-x

Cite this article as:
Farace, P., D’Ambrosio, D., Merigo, F. et al. Eur J Nucl Med Mol Imaging (2009) 36: 616. doi:10.1007/s00259-008-1012-x

Abstract

Purpose

To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees.

Methods

Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth.

Results

FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours.

Conclusion

Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging.

Keywords

FDGPETCarcinomaStromaRadiotherapy

Copyright information

© Springer-Verlag 2008