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 journalArticle

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

Fingerprint

Radiotherapy
Carcinoma
Neoplasms
Perfusion Imaging
Blood Vessels
Histology
Tumor Burden
Pancreatic Neoplasms
Nude Mice
Albumins
Prostatic Neoplasms
Perfusion
Immunohistochemistry
Magnetic Resonance Imaging
Glucose
Growth

Keywords

  • Carcinoma
  • FDG
  • PET
  • Radiotherapy
  • Stroma

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target. / Farace, Paolo; D'Ambrosio, Daniela; Merigo, Flavia; Galiè, Mirco; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano; Degrassi, Anna; Sbarbati, Andrea; Rubello, Domenico; Marzola, Pasquina.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 36, No. 4, 04.2009, p. 616-623.

Research output: Contribution to journalArticle

Farace, Paolo ; D'Ambrosio, Daniela ; Merigo, Flavia ; Galiè, Mirco ; Nanni, Cristina ; Spinelli, Antonello ; Fanti, Stefano ; Degrassi, Anna ; Sbarbati, Andrea ; Rubello, Domenico ; Marzola, Pasquina. / Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target. In: European Journal of Nuclear Medicine and Molecular Imaging. 2009 ; Vol. 36, No. 4. pp. 616-623.
@article{70f786131a3e414ebab0a9a182778d5d,
title = "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.",
keywords = "Carcinoma, FDG, PET, Radiotherapy, Stroma",
author = "Paolo Farace and Daniela D'Ambrosio and Flavia Merigo and Mirco Gali{\`e} and Cristina Nanni and Antonello Spinelli and Stefano Fanti and Anna Degrassi and Andrea Sbarbati and Domenico Rubello and Pasquina Marzola",
year = "2009",
month = "4",
doi = "10.1007/s00259-008-1012-x",
language = "English",
volume = "36",
pages = "616--623",
journal = "European Journal of Pediatrics",
issn = "0340-6199",
publisher = "Springer Berlin Heidelberg",
number = "4",

}

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

UR - http://www.scopus.com/inward/record.url?scp=62149089920&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62149089920&partnerID=8YFLogxK

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 -