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

Journal article

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.

Authors: Annovazzi, A; D'Alessandria, C; Bonanno, E; Mather, S; Cornelissen, B

• Publication status: Published
• Journal: European journal of nuclear medicine and molecular imaging
• Volume: 33
• Issue: 4
• Pages: 474-482
• Publication date: 2006-04-01
• DOI: 10.1007/s00259-005-0001-6
• EISSN: 1619-7089
• ISSN: 1619-7070
• Language: English
• Keywords: Mice; T-Lymphocytes; Interleukin-12; Tissue Distribution; Male; Isotope Labeling; Metabolic Clearance Rate; Radiopharmaceuticals; Organ Specificity; Organotechnetium Compounds; Animals; Cell Line; Colitis; Feasibility Studies