Skip to main content

Advertisement

SpringerLink
Log in

PET imaging of inflammation and adenocarcinoma xenografts using vascular adhesion protein 1 targeting peptide 68Ga-DOTAVAP-P1: comparison with 18F-FDG

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to evaluate inflammation and tumour imaging with a vascular adhesion protein 1 (VAP-1) targeting peptide 68Ga-DOTAVAP-P1 in comparison with 18F-FDG.

Methods

Rats with both subcutaneous human pancreatic adenocarcinoma xenografts and turpentine oil-induced acute sterile inflammation were evaluated by dynamic positron emission tomography (PET) and by digital autoradiography of tissue cryosections. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections.

Results

68Ga-DOTAVAP-P1 delineated acute, sterile inflammation comparable with 18F-FDG. However, the tumour uptake of 68Ga-DOTAVAP-P1 was low in contrast to prominent 18F-FDG uptake. The standardised uptake values of inflammation and tumours by PET were 1.1 ± 0.4 (mean ± SEM) and 0.4 ± 0.1 for 68Ga-DOTAVAP-P1 and 2.0 ± 0.5 and 1.6 ± 0.8 for 18F-FDG, respectively. In addition, PET studies showed inflammation to muscle and tumour to muscle ratios of 5.1 ± 3.1 and 1.7 ± 0.3 for 68Ga-DOTAVAP-P1 and 6.2 ± 0.7 and 4.6 ± 2.2 for 18F-FDG, respectively. Immunohistochemistry revealed increased expression of luminal VAP-1 on the endothelium at the site of inflammation and low expression in the tumour

Conclusion

The 68Ga-DOTAVAP-P1 PET was able to visualise inflammation better than tumour, which was in accordance with the luminal expression of VAP-1 on vasculature in these experimental models.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Smith DJ, Salmi M, Bono P, Hellman J, Leu T, Jalkanen S. Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule. J Exp Med 1998;188:17–27.

    Article  CAS  PubMed  Google Scholar 

  2. Salmi M, Jalkanen S. VAP-1: an adhesin and an enzyme. Trends Immunol 2001;22:211–6.

    Article  CAS  PubMed  Google Scholar 

  3. Tohka S, Laukkanen M-L, Jalkanen S, Salmi M. Vascular adhesion protein 1 (VAP-1) functions as a molecular brake during granulocyte rolling and mediates recruitment in vivo. FASEB J 2001;15:373–82.

    Article  CAS  PubMed  Google Scholar 

  4. Jalkanen S, Salmi M. VAP-1 and CD73, endothelial cell surface enzymes in leukocyte extravasation. Arterioscler Thromb Vasc Biol 2008;28:18–26.

    Article  CAS  PubMed  Google Scholar 

  5. Yoong KF, McNab G, Hübscher SG, Adams DH. Vascular adhesion protein-1 and ICAM-1 support the adhesion of tumor-infiltrating lymphocytes to tumor endothelium in human hepatocellular carcinoma. J Immunol 1998;160:3978–88.

    CAS  PubMed  Google Scholar 

  6. Irjala H, Salmi M, Alanen K, Grénman R, Jalkanen S. Vascular adhesion protein 1 mediates binding of immunotherapeutic effector cells to tumor endothelium. J Immunol 2001;166:6937–43.

    CAS  PubMed  Google Scholar 

  7. Marttila-Ichihara F, Auvinen K, Elima K, Jalkanen S, Salmi M. Vascular adhesion protein-1 enhances tumor growth by supporting recruitment of Gr-1+CD11b+ myeloid cells into tumors. Cancer Res 2009;69:7875–83.

    Article  CAS  PubMed  Google Scholar 

  8. Pauwels EK, Ribeiro MJ, Stoot JH, McCready VR, Bourguignon M, Mazière B. FDG accumulation and tumor biology. Nucl Med Biol 1998;25:317–22.

    Article  CAS  PubMed  Google Scholar 

  9. Younes M, Brown RW, Stephenson M, Gondo M, Cagle PT. Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer 1997;80:1046–51.

    Article  CAS  PubMed  Google Scholar 

  10. Lankinen P, Mäkinen TJ, Pöyhönen TA, Virsu P, Salomäki S, Hakanen AJ, et al. (68)Ga-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation in healing bones and the progress of infection in osteomyelitic bones. Eur J Nucl Med Mol Imaging 2008;35:352–64.

    Article  CAS  PubMed  Google Scholar 

  11. Ujula T, Salomäki S, Virsu P, Lankinen P, Mäkinen TJ, Autio A, et al. Synthesis, 68Ga labeling and preliminary evaluation of DOTA peptide binding vascular adhesion protein-1: a potential PET imaging agent for diagnosing osteomyelitis. Nucl Med Biol 2009;36:631–41.

    Article  CAS  PubMed  Google Scholar 

  12. Hamacher K, Coenen HH, Stöcklin G. Efficient stereospecific synthesis of no-carrier-added 2-[18F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med 1986;27:235–8.

    CAS  PubMed  Google Scholar 

  13. Mäkinen TJ, Lankinen P, Pöyhönen T, Jalava J, Aro HT, Roivainen A. Comparison of 18F-FDG and 68Ga PET imaging in the assessment of experimental osteomyelitis due to Staphylococcus aureus. Eur J Nucl Med Mol Imaging 2005;32:1259–68.

    Article  PubMed  Google Scholar 

  14. Ujula T, Salomäki S, Autio A, Luoto P, Tolvanen T, Lehikoinen P, et al. 68Ga-chloride PET reveals human pancreatic adenocarcinoma xenografts in rats—comparison with FDG. Mol Imaging Biol 2010;12:259–68. doi:10.1007/s11307-009-0267-3.

    Article  PubMed  Google Scholar 

  15. Yamada S, Kubota K, Kubota R, Ido T, Tamahashi N. High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med 1995;36:1301–6.

    CAS  PubMed  Google Scholar 

  16. van Waarde A, Cobben DC, Suurmeijer AJ, Maas B, Vaalburg W, de Vries EF, et al. Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model. J Nucl Med 2004;45:695–700.

    PubMed  Google Scholar 

  17. Suzuki M, Yamaguchi K, Honda G, Iwata R, Furumoto S, Jeong MG, et al. An experimental study on O-[18F]fluoromethyl-L-tyrosine for differentiation between tumor and inflammatory tissues. Ann Nucl Med 2005;19:589–95.

    Article  CAS  PubMed  Google Scholar 

  18. Kubota K, Furumoto S, Iwata R, Fukuda H, Kawamura K, Ishiwata K. Comparison of 18F-fluoromethylcholine and 2-deoxy-D-glucose in the distribution of tumor and inflammation. Ann Nucl Med 2006;20:527–33.

    Article  CAS  PubMed  Google Scholar 

  19. Zhao S, Kuge Y, Kohanawa M, Takahashi T, Zhao Y, Yi M, et al. Usefulness of 11C-methionine for differentiating tumors from granulomas in experimental rat models: a comparison with 18F-FDG and 18F-FLT. J Nucl Med 2008;49:135–41.

    Article  CAS  PubMed  Google Scholar 

  20. Tan MH, Nowak NJ, Loor R, Ochi H, Sandberg AA, Lopez C, et al. Characterization of a new primary human pancreatic tumor line. Cancer Invest 1986;4:15–23.

    Article  CAS  PubMed  Google Scholar 

  21. Lalor PF, Edwards S, McNab G, Salmi M, Jalkanen S, Adams D. Vascular adhesion protein-1 mediates adhesion and transmigration of lymphocytes on human hepatic endothelial cells. J Immunol 2002;169:983–92.

    CAS  PubMed  Google Scholar 

  22. Farace P, D’Ambrosio D, Merigo F, Galiè M, Nanni C, Spinelli A, 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 2009;36:616–23.

    Article  PubMed  Google Scholar 

  23. Nakao A, Fujii T, Sugimoto H, Kanazumi N, Nomoto S, Kodera Y, et al. Oncological problems in pancreatic cancer surgery. World J Gastroenterol 2006;12:4466–72.

    PubMed  Google Scholar 

  24. Saif MW, Cornfeld D, Modarresifar H, Ojha B. 18F-FDG positron emission tomography CT (FDG PET-CT) in the management of pancreatic cancer: initial experience in 12 patients. J Gastrointestin Liver Dis 2008;17:173–8.

    PubMed  Google Scholar 

  25. Nakata B, Nishimura S, Ishikawa T, Ohira M, Nishino H, Kawabe J, et al. Prognostic predictive value of 18F-fluorodeoxyglucose positron emission tomography for patients with pancreatic cancer. Int J Oncol 2001;19:53–8.

    CAS  PubMed  Google Scholar 

  26. Sperti C, Pasquali C, Chierichetti F, Ferronato A, Decet G, Pedrazzoli S. 18-Fluorodeoxyglucose positron emission tomography in predicting survival of patients with pancreatic carcinoma. J Gastrointest Surg 2003;7:953–9.

    Article  PubMed  Google Scholar 

  27. Lyshchik A, Higashi T, Nakamoto Y, Fujimoto K, Doi R, Imamura M, et al. Dual-phase 18F-fluoro-2-deoxy-D-glucose positron emission tomography as a prognostic parameter in patients with pancreatic cancer. Eur J Nucl Med Mol Imaging 2005;32:389–97.

    Article  PubMed  Google Scholar 

  28. van Kouwen MC, Jansen JB, van Goor H, de Castro S, Oyen WJ, Drenth JP. FDG-PET is able to detect pancreatic carcinoma in chronic pancreatitis. Eur J Nucl Med Mol Imaging 2005;32:399–404.

    Article  PubMed  Google Scholar 

  29. Hoffman EJ, Huang SC, Phelps ME. Quantitation in positron emission computed tomography: 1. Effect of object size. J Comput Assist Tomogr 1979;3:299–308.

    Article  CAS  PubMed  Google Scholar 

  30. Visvikis D, Cheze-LeRest C, Costa DC, Bomanji J, Gacinovic S, Ell PJ. Influence of OSEM and segmented attenuation correction in the calculation of standardised uptake values for [18F]FDG PET. Eur J Nucl Med 2001;28:1326–35.

    Article  CAS  PubMed  Google Scholar 

  31. Boellaard R, van Lingen A, Lammertsma AA. Experimental and clinical evaluation of iterative reconstruction (OSEM) in dynamic PET: quantitative characteristics and effects on kinetic modeling. J Nucl Med 2001;42:808–17.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Sari Mäki is thanked for excellent assistance in immunohistochemistry and Henri Sipilä for 68Ga chemistry. Ville Aalto is thanked for the expertise in statistical analysis and Jouko Sandholm for assistance in microscopy. The study was conducted within the Finnish Centre of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research supported by the Academy of Finland, the University of Turku, the Turku University Hospital and the Åbo Akademi University. The study was further supported by grants from the Turku University Hospital (EVO grants, A.R. and A.A) and from the Academy of Finland (grant no. 119048, A.R). Anu Autio and Tiina Ujula are Ph.D. students supported by the Drug Discovery Graduate School.

Author information

Authors and Affiliations

  1. Turku PET Centre, University of Turku and Turku University Hospital, 20521, Turku, Finland

    Anu Autio, Tiina Ujula, Pauliina Luoto, Satu Salomäki & Anne Roivainen

  2. Department of Chemistry, University of Turku, Turku, Finland

    Satu Salomäki

  3. MediCity Research Laboratory, University of Turku, Turku, Finland

    Sirpa Jalkanen

  4. National Public Health Institute, Turku, Finland

    Sirpa Jalkanen

  5. Turku Centre for Disease Modeling, University of Turku, Turku, Finland

    Anne Roivainen

Authors
  1. Anu Autio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiina Ujula
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pauliina Luoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satu Salomäki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sirpa Jalkanen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anne Roivainen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Roivainen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Autio, A., Ujula, T., Luoto, P. et al. PET imaging of inflammation and adenocarcinoma xenografts using vascular adhesion protein 1 targeting peptide 68Ga-DOTAVAP-P1: comparison with 18F-FDG. Eur J Nucl Med Mol Imaging 37, 1918–1925 (2010). https://doi.org/10.1007/s00259-010-1497-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-010-1497-y

Keywords

Search

Navigation