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

Eur J Nucl Med Mol Imaging. 2006 Apr;33(4):474-82. doi: 10.1007/s00259-005-0001-6. Epub 2006 Jan 27.


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 Th(1) lymphocytes. The aims of the present study were to label IL12 with (99m)Tc, 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( 99m)Tc. An in vitro binding assay was performed on KIT225 cells, an IL12 receptor-positive cell line. (99m)Tc-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: (99m)Tc-IL12 labelling efficiency ranged between 75% and 85%. Saturation binding analysis revealed a K (d) 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, (99m)Tc-IL12-specific uptake in these cells increased over time. (99m)Tc-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Colitis / diagnostic imaging*
  • Colitis / metabolism*
  • Colitis / pathology
  • Feasibility Studies
  • Interleukin-12
  • Isotope Labeling / methods
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Organ Specificity
  • Organotechnetium Compounds
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / diagnostic imaging*
  • T-Lymphocytes / metabolism*
  • Tissue Distribution


  • 99mTc-HYNIC-interleukin-12
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Interleukin-12