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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.

Original publication

DOI

10.1007/s00259-005-0001-6

Type

Journal article

Journal

Eur J Nucl Med Mol Imaging

Publication Date

04/2006

Volume

33

Pages

474 - 482

Keywords

Animals, Cell Line, Colitis, Feasibility Studies, Interleukin-12, Isotope Labeling, Male, Metabolic Clearance Rate, Mice, Organ Specificity, Organotechnetium Compounds, Radionuclide Imaging, Radiopharmaceuticals, T-Lymphocytes, Tissue Distribution