title: Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Morphological-Biomedical Sciences, University of Verona, Verona, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Farace
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Ambrosio
authors.forename: Flavia
authors.initials: F
authors.lastname: Merigo
authors.forename: Mirco
authors.initials: M
authors.lastname: Galiè
authors.forename: Cristina
authors.initials: C
authors.lastname: Nanni
authors.forename: Antonello
authors.initials: A
authors.lastname: Spinelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Fanti
authors.forename: Anna
authors.initials: A
authors.lastname: Degrassi
authors.forename: Andrea
authors.initials: A
authors.lastname: Sbarbati
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.forename: Pasquina
authors.initials: P
authors.lastname: Marzola
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000175:diagnosis* / Q000000981:diagnostic imaging; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis; D006720:Homozygote; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography; D019275:Radiopharmaceuticals / Q000494:pharmacology*
chemical_list: D051272:Glucose Transporter Type 1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019275:Radiopharmaceuticals; C495678:Slc2a1 protein, mouse; D019788:Fluorodeoxyglucose F18