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.

Annovazzi, A., D'Alessandria, C., Bonanno, E., Mather, S., Cornelissen, B., Van De Wiele, C., et al. (2006). Synthesis of Tc-99m-HYNIC-interleukin-12, a new specific radiopharmaceutical for imaging T lymphocytes. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 33(4), 474-482 [10.1007/s00259-005-0001-6].

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

BONANNO, ELENA;MATTEI, MAURIZIO;PALMIERI, GIAMPIERO;
2006-01-01

Abstract

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/08 - Anatomia Patologica
English
interleukin-12; T lymphocytes; HYNIC; molecular imaging
Annovazzi, A., D'Alessandria, C., Bonanno, E., Mather, S., Cornelissen, B., Van De Wiele, C., et al. (2006). Synthesis of Tc-99m-HYNIC-interleukin-12, a new specific radiopharmaceutical for imaging T lymphocytes. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 33(4), 474-482 [10.1007/s00259-005-0001-6].
Annovazzi, A; D'Alessandria, C; Bonanno, E; Mather, S; Cornelissen, B; Van De Wiele, C; Dierckx, R; Mattei, M; Palmieri, G; Scopinaro, F; Signore, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/34653
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