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 Tc-99m, 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)pTc. An in vitro binding assay was performed on KIT225 cells, an IL12 receptor-positive cell line. Tc-99m-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: Tc-99m-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)supercript stopTc-IL12-specific uptake in these cells increased over time. Tc-99m-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.
|Number of pages||9|
|Journal||European Journal of Nuclear Medicine and Molecular Imaging|
|Publication status||Published - Apr-2006|
- T lymphocytes
- molecular imaging
- RECOMBINANT HUMAN INTERLEUKIN-12
- RENAL-CELL CARCINOMA
- PHASE-I TRIAL
- IL-12 RECEPTOR