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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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Authors and Affiliations

  1. Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona, Italy

    Paolo Farace, Flavia Merigo, Mirco Galiè, Andrea Sbarbati & Pasquina Marzola

  2. Department of Nuclear Medicine, Policlinico ‘S. Orsola-Malpighi’, Bologna, Italy

    Daniela D’Ambrosio, Cristina Nanni, Antonello Spinelli & Stefano Fanti

  3. Nerviano Medical Sciences, Milan, Italy

    Anna Degrassi

  4. PET Centre, Department of Nuclear Medicine, ‘S. Maria della Misericordia’ Hospital, Viale Tre Martiri 140, 45100, Rovigo, Italy

    Domenico Rubello

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  1. Paolo Farace
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  2. Daniela D’Ambrosio
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  3. Flavia Merigo
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Correspondence to Domenico Rubello.

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Farace, P., D’Ambrosio, D., Merigo, F. et al. Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target. Eur J Nucl Med Mol Imaging 36, 616–623 (2009). https://doi.org/10.1007/s00259-008-1012-x

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  • DOI: https://doi.org/10.1007/s00259-008-1012-x

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