Contributions
Abstract: P1066
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Background: The murine Experimental Autoimmune Encephalomyelitis (EAE) model is well-characterised for preclinical evaluation of MS therapeutics. We evaluated the biodistribution of a novel zirconium-89 (89Zr) labelled anti-CD20 antibody within the central nervous system (CNS) and in lymphatic compartments.
Objectives: To investigate subcutaneous (s.c.) administration of 89Zr-anti-CD20 antibody, and to compare imaging and biodistribution in control (sham-injected) and EAE-variant C57BL/6 mouse model.
Methods: A novel rhMOG-induced EAE variant was generated in C57BL/6 mice. Lesion topography was mapped using standard histological approaches and parameters of neuroinflammation (B- and T-cell infiltration, demyelination and microglial reactivity) were evaluated by immunohistochemistry. Biodistribution of 89Zr-anti-CD20 antibody in control and EAE mice following s.c. right lower flank injection was assessed using positron emission tomography-computed tomography (PET-CT) and gamma counting of excised organs at early (24h) and later (72h and 7 days) time points. We evaluated the distribution of tracer in deep cervical, mandibular and caudal lymph node groups and CNS compartments (spinal cord, medulla, pons and cerebellum).
Results: The clinical severity of EAE was moderate. Spatio-temporal mapping identified reproducible lesion topography along the whole of the neuraxis, associated with B- and T-cell infiltration together with severe demyelination and microglial reactivity. On PET-CT imaging, the proportion of 89Zr-anti-CD20 antibody remaining in the whole body at 7 days following s.c. injection was comparable between control (55±4%) and EAE (58±9%) mice. Gamma counting data at early time points showed that 89Zr-anti-CD20 antibody levels were highest in the draining lymph nodes, spleen, circulating blood and in highly perfused organs in both control and EAE mice. In draining lymph nodes, peak tracer uptake occurred earlier in EAE (24h) than in control mice (72h).
Conclusions: Subcutaneously administered 89Zr-anti-CD20 antibody is effectively absorbed from the injection site and is distributed preferentially to draining lymph nodes, spleen and blood in both control and EAE mice. Furthermore, differential uptake of tracer in lymphatic and CNS compartments associated with MS lesions occurred in EAE mice. The subcutaneous administration of anti-CD20 antibody enables targeting to the relevant tissues.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
David Reutens' institution (The University of Queensland) has received research support from Novartis, BGI, and Innate.
The institution (The University of Queensland) of Mary-Anne Migotto, Rajiv Bhalla and Karine Mardon received research support from Novartis.
Jacqueline Orian received personal compensation for serving as Associate Editor for Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments.
Current Topics in Behavioral Neurosciences, Vol 26, Springer De, and has received research support from Novartis.
Gisbert Weckbecker and Rainer Kneuer are employees of Novartis.
Abstract: P1066
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Experimental models
Background: The murine Experimental Autoimmune Encephalomyelitis (EAE) model is well-characterised for preclinical evaluation of MS therapeutics. We evaluated the biodistribution of a novel zirconium-89 (89Zr) labelled anti-CD20 antibody within the central nervous system (CNS) and in lymphatic compartments.
Objectives: To investigate subcutaneous (s.c.) administration of 89Zr-anti-CD20 antibody, and to compare imaging and biodistribution in control (sham-injected) and EAE-variant C57BL/6 mouse model.
Methods: A novel rhMOG-induced EAE variant was generated in C57BL/6 mice. Lesion topography was mapped using standard histological approaches and parameters of neuroinflammation (B- and T-cell infiltration, demyelination and microglial reactivity) were evaluated by immunohistochemistry. Biodistribution of 89Zr-anti-CD20 antibody in control and EAE mice following s.c. right lower flank injection was assessed using positron emission tomography-computed tomography (PET-CT) and gamma counting of excised organs at early (24h) and later (72h and 7 days) time points. We evaluated the distribution of tracer in deep cervical, mandibular and caudal lymph node groups and CNS compartments (spinal cord, medulla, pons and cerebellum).
Results: The clinical severity of EAE was moderate. Spatio-temporal mapping identified reproducible lesion topography along the whole of the neuraxis, associated with B- and T-cell infiltration together with severe demyelination and microglial reactivity. On PET-CT imaging, the proportion of 89Zr-anti-CD20 antibody remaining in the whole body at 7 days following s.c. injection was comparable between control (55±4%) and EAE (58±9%) mice. Gamma counting data at early time points showed that 89Zr-anti-CD20 antibody levels were highest in the draining lymph nodes, spleen, circulating blood and in highly perfused organs in both control and EAE mice. In draining lymph nodes, peak tracer uptake occurred earlier in EAE (24h) than in control mice (72h).
Conclusions: Subcutaneously administered 89Zr-anti-CD20 antibody is effectively absorbed from the injection site and is distributed preferentially to draining lymph nodes, spleen and blood in both control and EAE mice. Furthermore, differential uptake of tracer in lymphatic and CNS compartments associated with MS lesions occurred in EAE mice. The subcutaneous administration of anti-CD20 antibody enables targeting to the relevant tissues.
Disclosure: This study was funded by Novartis Pharma AG, Basel, Switzerland.
David Reutens' institution (The University of Queensland) has received research support from Novartis, BGI, and Innate.
The institution (The University of Queensland) of Mary-Anne Migotto, Rajiv Bhalla and Karine Mardon received research support from Novartis.
Jacqueline Orian received personal compensation for serving as Associate Editor for Emerging and Evolving Topics in Multiple Sclerosis Pathogenesis and Treatments.
Current Topics in Behavioral Neurosciences, Vol 26, Springer De, and has received research support from Novartis.
Gisbert Weckbecker and Rainer Kneuer are employees of Novartis.