Synthesis of Tc-99m-HYNIC-interleukin-12, a new specific radiopharmaceutical for imaging T lymphocytes
| Autor: | Christophe Van de Wiele, Alberto Signore, Graziana Palmieri, Calogero D'Alessandria, Bart Cornelissen, Francesco Scopinaro, Rudi Dierckx, Maurizio Mattei, Elena Bonanno, Alessio Annovazzi, Stephen J. Mather |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
HYNIC interleukin-12 medicine.medical_treatment Lymphocyte T-Lymphocytes MELANOMA T lymphocytes molecular imaging Mice PHASE-I TRIAL RENAL-CELL CARCINOMA Medicine Tissue Distribution Animals Cell Line Colitis metabolism/pathology/radionuclide imaging Feasibility Studies Interleukin-12 Isotope Labeling methods Metabolic Clearance Rate Organ Specificity Organotechnetium Compounds Radiopharmaceuticals chemical synthesis/diagnostic use/pharmacokinetics chemistry/metabolism/radionuclide imaging Melanoma General Medicine IL-12 RECEPTOR CROHNS-DISEASE Cytokine medicine.anatomical_structure Interleukin 12 RECOMBINANT HUMAN INTERLEUKIN-12 Biodistribution Settore MED/08 - Anatomia Patologica AUTOIMMUNE-DISEASES I-123-INTERLEUKIN-2 Radiology Nuclear Medicine and imaging Radionuclide Imaging Settore MED/04 - Patologia Generale business.industry medicine.disease In vitro CYTOKINE Immunology SCINTIGRAPHY Molecular imaging business |
| Zdroj: | European Journal of Nuclear Medicine and Molecular Imaging, 33(4), 474-482. SPRINGER |
| ISSN: | 1619-7070 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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