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

A Annovazzi, C D'Alessandria, E Bonanno, SJ Mather, B Cornelissen, C van de Wiele, RA Dierckx, M Mattei, G Palmieri, F Scopinaro, A Signore*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    27 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)474-482
    Number of pages9
    JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
    Issue number4
    Publication statusPublished - Apr-2006


    • interleukin-12
    • T lymphocytes
    • HYNIC
    • molecular imaging
    • IL-12 RECEPTOR
    • I-123-INTERLEUKIN-2

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