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

G. Malviya*, K. L. Anzola, E. Podesta, B. Lagana, C. Del Mastro, R. A. Dierckx, F. Scopinaro, A. Signore

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Scopus)

Abstract

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.

Rituximab was labelled with Tc-99m via 2-ME reduction method. In vitro quality controls of Tc-99m-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 mu g) of Tc-99m-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.

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 Tc-99m-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 Sjogren's syndrome, Beh double dagger et'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 Beh double dagger et'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.

Rituximab can be efficiently labelled with Tc-99m 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.

Original languageEnglish
Pages (from-to)637-646
Number of pages10
JournalMolecular Imaging and Biology
Volume14
Issue number5
DOIs
Publication statusPublished - Oct-2012

Keywords

  • Rituximab
  • Anti-CD20 antibody
  • Radiolabelling
  • Molecular imaging
  • Therapy decision making
  • RADIOLABELED MONOCLONAL-ANTIBODIES
  • RHEUMATOID-ARTHRITIS
  • CLASSIFICATION CRITERIA
  • REVISED CRITERIA
  • CELL ACTIVATION
  • PATHOGENESIS
  • MECHANISMS
  • ANTIGEN

Cite this