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Mol Imaging Biol ; 14(5): 637-46, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22127469

RESUMO

PURPOSE: The rationale of the present study was to radiolabel rituximab with 99m-technetium and to image B lymphocytes infiltration in the affected tissues of patients with chronic inflammatory autoimmune diseases, in particular, the candidates to be treated with unlabelled rituximab, in order to provide a rationale for 'evidence-based' therapy. PROCEDURES: Rituximab was labelled with (99m)Tc via 2-ME reduction method. In vitro quality controls of (99m)Tc-rituximab included stability assay, cysteine challenge, SDS-PAGE, immunoreactive fraction assay and competitive binding assay on CD20+ve Burkitt lymphoma-derived cells. For the human pilot study, 350-370 MBq (100 µg) of (99m)Tc-rituximab were injected in 20 patients with different chronic inflammatory autoimmune diseases. Whole body anteroposterior planar scintigraphic images were acquired 6 and 20 h p.i. RESULTS: Rituximab was labelled to a high labelling efficiency (>98%) and specific activity (3515-3700 MBq/mg) with retained biochemical integrity, stability and biological activity. Scintigraphy with (99m)Tc-rituximab in patients showed a rapid and persistent spleen uptake, and the kidney appeared to be a prominent source for the excretion of radioactivity. Inflamed joints showed a variable degree of uptake at 6 h p.i. in patients with rheumatoid arthritis indicating patient variability; similarly, the salivary and lacrimal glands showed variable uptake in patients with Sjögren's syndrome, Behçet's disease and sarcoidosis. Inflammatory disease with particular characteristics showed specific uptake in inflammatory lesions, such as, dermatopolymyositis patients showed moderate to high skin uptake, a sarcoidosis patient showed moderate lung uptake, a Behçet's disease patient showed high oral mucosa uptake and a polychondritis patient showed moderate uptake in neck cartilages. In one patient with systemic lupus erythematosus, we did not find any non-physiological uptake. CONCLUSION: Rituximab can be efficiently labelled with (99m)Tc with high labelling efficiency. The results suggest that this technique might be used to assess B lymphocyte infiltration in affected organs in patients with autoimmune diseases; this may provide a rationale for anti-CD20 therapies.


Assuntos
Anticorpos Monoclonais Murinos , Doenças Autoimunes/diagnóstico por imagem , Linfócitos B/diagnóstico por imagem , Linfócitos B/patologia , Diagnóstico por Imagem/métodos , Inflamação/diagnóstico por imagem , Marcação por Isótopo , Compostos de Organotecnécio , Anticorpos Monoclonais Murinos/sangue , Doenças Autoimunes/complicações , Doenças Autoimunes/patologia , Ligação Competitiva , Estabilidade de Medicamentos , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Inflamação/complicações , Masculino , Pessoa de Meia-Idade , Compostos de Organotecnécio/sangue , Cintilografia , Rituximab
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