TY - JOUR
T1 - Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target
AU - Farace, Paolo
AU - D'Ambrosio, Daniela
AU - Merigo, Flavia
AU - Galiè, Mirco
AU - Nanni, Cristina
AU - Spinelli, Antonello
AU - Fanti, Stefano
AU - Degrassi, Anna
AU - Sbarbati, Andrea
AU - Rubello, Domenico
AU - Marzola, Pasquina
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
KW - Carcinoma
KW - FDG
KW - PET
KW - Radiotherapy
KW - Stroma
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U2 - 10.1007/s00259-008-1012-x
DO - 10.1007/s00259-008-1012-x
M3 - Article
C2 - 19093111
AN - SCOPUS:62149089920
VL - 36
SP - 616
EP - 623
JO - European Journal of Pediatrics
JF - European Journal of Pediatrics
SN - 0340-6199
IS - 4
ER -