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FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

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

Abstract

Purpose

The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype.

Methods

Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry.

Results

Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal—but not acinar—tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma.

Conclusion

In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours.

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Acknowledgements

We are very grateful to Dr. Eric P. Sandgren for providing Ela1-myc mice and Dr. Chaitanya R. Divgi for critical reading of the manuscript. We also thank S. Mancilla, T. Lobato and A. Doutres for technical support and the personnel of the Radiochemistry Laboratory of IAT for FDG manufacture. This study was partially supported by the RTICC (Instituto de Salud Carlos III) and by grants from Plan Nacional de I + D, Ministerio de Educación y Ciencia (SAF2005-00704), Fundació La Marató TV3 (grant 051110) and Generalitat de Catalunya (2005SGR00729) to PN and from Plan Nacional de I + D, Ministerio de Educación y Ciencia (SAF2004-01137) and VIth Framework WU Programme (Biomed Programme (LSHB-CT-2006-018771 MOLDIAG-PaCa) to FXR. IA was partially supported by a postdoctoral fellowship from the Basque Government.

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Authors and Affiliations

  1. Institut Municipal d’Investigació Mèdica-Hospital del Mar, Parc de Recerca Biomèdica de Barcelona, Carrer del Dr. Aiguader, 88, 08003, Barcelona, Spain

    Ibane Abasolo, Judit Pujal, Pilar Navarro & Francisco X. Real

  2. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Carrer del Dr. Aiguader, 88, 08003, Barcelona, Spain

    Ibane Abasolo & Francisco X. Real

  3. Institut d’Alta Tecnologia - CRC, Parc de Recerca Biomèdica de Barcelona, Carrer del Dr. Aiguader 88, 08003, Barcelona, Spain

    Ibane Abasolo & Olga Millán

  4. Departament de Medicina i Cirurgia Animals, Universitat Autònoma de Barcelona, 08193, Bellaterra (Cerdanyola del Valles), Barcelona, Spain

    Rosa M. Rabanal & Anna Serafin

  5. Programa de Patología Molecular, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro, 3, 28029, Madrid, Spain

    Francisco X. Real

Authors
  1. Ibane Abasolo
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  2. Judit Pujal
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  3. Rosa M. Rabanal
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  7. Francisco X. Real
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Correspondence to Francisco X. Real.

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Abasolo, I., Pujal, J., Rabanal, R.M. et al. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours. Eur J Nucl Med Mol Imaging 36, 1156–1166 (2009). https://doi.org/10.1007/s00259-009-1083-3

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  • DOI: https://doi.org/10.1007/s00259-009-1083-3

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