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Published in: Molecular Imaging and Biology 5/2012

Open Access 01-10-2012 | Research Article

99mTc-labeled Rituximab for Imaging B Lymphocyte Infiltration in Inflammatory Autoimmune Disease Patients

Authors: G. Malviya, K. L. Anzola, E. Podestà, B. Laganà, C. Del Mastro, R. A. Dierckx, F. Scopinaro, A. Signore

Published in: Molecular Imaging and Biology | Issue 5/2012

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Abstract

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 99mTc via 2-ME reduction method. In vitro quality controls of 99mTc-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 99mTc-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 99mTc-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 99mTc 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.
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Metadata
Title
99mTc-labeled Rituximab for Imaging B Lymphocyte Infiltration in Inflammatory Autoimmune Disease Patients
Authors
G. Malviya
K. L. Anzola
E. Podestà
B. Laganà
C. Del Mastro
R. A. Dierckx
F. Scopinaro
A. Signore
Publication date
01-10-2012
Publisher
Springer-Verlag
Published in
Molecular Imaging and Biology / Issue 5/2012
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-011-0527-x

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