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

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.

• Authors: Paolo Farace, Daniela D'Ambrosio, Flavia Merigo, Mirco Galiè, Cristina Nanni, Antonello Spinelli, Stefano Fanti, Anna Degrassi, Andrea Sbarbati, Domenico Rubello, Pasquina Marzola
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 36 Issue 4 Pg. 616-23 (Apr 2009) ISSN: 1619-7089 [Electronic] Germany
• PMID: 19093111 (Publication Type: Journal Article)

Chemical References

• Glucose Transporter Type 1
• Platelet Endothelial Cell Adhesion Molecule-1
• Radiopharmaceuticals
• Slc2a1 protein, mouse
• Fluorodeoxyglucose F18

Topics

• Animals
• Carcinoma (diagnosis, diagnostic imaging)
• Cell Line, Tumor
• Fluorodeoxyglucose F18 (pharmacology)
• Glucose Transporter Type 1 (biosynthesis)
• Homozygote
• Humans
• Image Processing, Computer-Assisted
• Immunohistochemistry (methods)
• Mice
• Mice, Nude
• Neoplasms (diagnosis, diagnostic imaging)
• Platelet Endothelial Cell Adhesion Molecule-1 (biosynthesis)
• Positron-Emission Tomography (methods)
• Radiography
• Radiopharmaceuticals (pharmacology)