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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)616-623
Number of pages8
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume36
Issue number4
DOIs
Publication statusPublished - Apr 2009

Keywords

  • Carcinoma
  • FDG
  • PET
  • Radiotherapy
  • Stroma

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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