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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02437

Efficient distribution of a Novel Zirconium-89 Labeled Anti-CD20 Antibody Following Subcutaneous and Intravenous Administration in Control and Experimental Autoimmune Encephalomyelitis-Variant Mice

 Mary-Anne Migotto1, Karine Mardon1, 2, Jacquie Orian3,  Gisbert Weckbecker4, Rainer Kneuer4,  Rajiv Bhalla1* and  David Reutens1, 5*
  • 1Centre for Advanced Imaging, University of Queensland, Australia
  • 2The University of Queensland, National Imaging Facility, Australia
  • 3La Trobe Institute for Molecular Science, La Trobe University, Australia
  • 4Novartis (Switzerland), Switzerland
  • 5University of Queensland, Australia

Objective: To investigate the imaging and biodistribution of a novel zirconium-89 (89Zr)-labeled mouse anti-CD20 monoclonal antibody (mAb) in control and experimental autoimmune encephalomyelitis (EAE) mice following subcutaneous (s.c.) and intravenous (i.v.) administration.
Background: Anti-CD20-mediated B-cell depletion using mAbs is a promising therapy for multiple sclerosis. Recombinant human myelin oligodendrocyte glycoprotein (rhMOG)-induced EAE involves B-cell-mediated inflammation and demyelination in mice.
Design/Methods: C57BL/6J mice (n=39) were EAE-induced using rhMOG. On Day 14 post EAE induction, 89Zr-labeled-anti-CD20 mAb was injected in control and EAE mice in the right lower flank (s.c.) or tail vein (i.v.). Positron emission tomography/computed tomography (PET/CT) imaging and gamma counting (ex vivo) were performed on Days 1, 3 and 7 to quantify tracer accumulation in the major organs, lymphatics, and central nervous system (CNS). A preliminary study was conducted in healthy mice to elucidate full and early kinetics of the tracer that were subsequently applied in the EAE and control mice study.
Results: 89Zr-labeled anti-CD20 mAb was effectively absorbed from s.c. and i.v. injection sites and distributed to all major organs in the EAE and control mice. There was a good correlation between in vivo PET/CT data and ex vivo quantification of biodistribution of the tracer. From gamma counting studies, initial tracer uptake within the lymphatic system was found to be higher in the draining lymph nodes (inguinal or subiliac and sciatic) following s.c. versus i.v. administration; within the CNS a significantly higher tracer uptake was observed at 24 hours in the cerebellum, cerebrum and thoracic spinal cord (p<0.05 for all) following s.c. versus i.v. administration.
Conclusions: The preclinical data suggest that initial tracer uptake was significantly higher in the draining lymph nodes (subiliac and sciatic) and parts of CNS (the cerebellum and cerebrum) when administered s.c. compared with i.v in EAE mice.

Keywords: Radiolabeling, positron emission tomography imaging (PET), Monoclonal antibody, Neuroimaging, biodistribution, Experimental autoimmune encephalomyelitis (EAE), Subcutaneous (SC), Intravenous (IV)

Received: 24 Jun 2019; Accepted: 30 Sep 2019.

Copyright: © 2019 Migotto, Mardon, Orian, Weckbecker, Kneuer, Bhalla and Reutens. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Rajiv Bhalla, Centre for Advanced Imaging, University of Queensland, Brisbane, 4072, Queensland, Australia, r.bhalla@uq.edu.au
Dr. David Reutens, University of Queensland, Brisbane, Australia, d.reutens@uq.edu.au