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

  • Paolo Farace
  • Daniela D’Ambrosio
  • Flavia Merigo
  • Mirco Galiè
  • Cristina Nanni
  • Antonello Spinelli
  • Stefano Fanti
  • Anna Degrassi
  • Andrea Sbarbati
  • Domenico Rubello
  • Pasquina Marzola
Original Article

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

FDG PET Carcinoma Stroma Radiotherapy 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Paolo Farace
    • 1
  • Daniela D’Ambrosio
    • 2
  • Flavia Merigo
    • 1
  • Mirco Galiè
    • 1
  • Cristina Nanni
    • 2
  • Antonello Spinelli
    • 2
  • Stefano Fanti
    • 2
  • Anna Degrassi
    • 3
  • Andrea Sbarbati
    • 1
  • Domenico Rubello
    • 4
  • Pasquina Marzola
    • 1
  1. 1.Department of Morphological-Biomedical Sciences, Section of Anatomy and HistologyUniversity of VeronaVeronaItaly
  2. 2.Department of Nuclear MedicinePoliclinico ‘S. Orsola-Malpighi’BolognaItaly
  3. 3.Nerviano Medical SciencesMilanItaly
  4. 4.PET Centre, Department of Nuclear Medicine‘S. Maria della Misericordia’ HospitalRovigoItaly

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