European Journal of Nuclear Medicine and Molecular Imaging

, Volume 33, Issue 4, pp 474–482

Synthesis of 99mTc-HYNIC-interleukin-12, a new specific radiopharmaceutical for imaging T lymphocytes

Authors

  • Alessio Annovazzi
    • Nuclear MedicineOspedale S. Andrea, 2nd Faculty of Medicine “La Sapienza”
    • Department of Nuclear MedicineUniversity of Groningen
  • Calogero D’Alessandria
    • Nuclear MedicineOspedale S. Andrea, 2nd Faculty of Medicine “La Sapienza”
  • Elena Bonanno
    • Department of Biopathology and Diagnostic ImagingUniversity “Tor Vergata”
  • Stephen J. Mather
    • Cancer Research UKSt. Bartholomew’s Hospital
  • Bart Cornelissen
    • Division of Nuclear MedicineUniversity of Gent
  • Christophe van de Wiele
    • Division of Nuclear MedicineUniversity of Gent
  • Rudi A. Dierckx
    • Department of Nuclear MedicineUniversity of Groningen
  • Maurizio Mattei
    • Department of BiologyNSTA, University “Tor Vergata”
  • Graziana Palmieri
    • Department of BiologyNSTA, University “Tor Vergata”
  • Francesco Scopinaro
    • Nuclear MedicineOspedale S. Andrea, 2nd Faculty of Medicine “La Sapienza”
    • Nuclear MedicineOspedale S. Andrea, 2nd Faculty of Medicine “La Sapienza”
    • Department of Nuclear MedicineUniversity of Groningen
Original article

DOI: 10.1007/s00259-005-0001-6

Cite this article as:
Annovazzi, A., D’Alessandria, C., Bonanno, E. et al. Eur J Nucl Med Mol Imaging (2006) 33: 474. doi:10.1007/s00259-005-0001-6

Abstract

Purpose

Few radiopharmaceuticals have been described for the study of lymphocyte trafficking despite its high clinical relevance. The main difficulty resides in the identification of a suitable highly specific probe to target these cells. Interleukin-12 (IL12) is a heterodimeric cytokine which plays a key role in the development of Th1 lymphocytes. The aims of the present study were to label IL12 with 99mTc, to evaluate its ability to bind to activated T lymphocytes in vitro and to study its biodistribution in normal mice and mice affected by autoimmune colitis.

Methods

IL12 was derivatised with HYNIC-NHS and labelled with 99mTc. An in vitro binding assay was performed on KIT225 cells, an IL12 receptor-positive cell line. 99mTc-IL12 biodistribution in normal mice was studied. Targeting experiments were performed in Balb/c mice injected with KIT225 cells and in mice with chemically induced chronic colitis.

Results

99mTc-IL12 labelling efficiency ranged between 75% and 85%. Saturation binding analysis revealed a Kd of 2.09 nM. Results of biodistribution studies showed a predominant hepatic route of excretion. A significant degree of uptake in the spleen and thymus was also observed. In mice injected with KIT225 cells, 99mTc-IL12-specific uptake in these cells increased over time. 99mTc-IL12 also accumulated significantly in bowel of mice affected by TNBS-induced colitis showing T lymphocyte infiltration at histology, while accumulation in colon from control animals was negligible.

Conclusion

We conclude that this radiolabelled cytokine is a suitable candidate for specific in vivo imaging of T lymphocytes: a step forward in molecular imaging of immune-mediated processes.

Keywords

Interleukin-12T lymphocytesHYNICMolecular imaging

Copyright information

© Springer-Verlag 2006