ArticleRespiratory research2026
SPECT as a translational non-invasive method to assess occupancy of the tissue transglutaminase-2 by zampilimab in the mouse lung.
Article in Respiratory research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundZampilimab is a humanized monoclonal antibody that selectively inhibits transamidation of human tissue transglutaminase-2 (hTG2), an enzymatic activity implicated in the development of Idiopathic Pulmonary Fibrosis (IPF). Since measuring target occupancy (TO) non-invasively in the lung is challenging, in this study, we evaluated the feasibility to radiolabel zampilimab and longitudinally measure its TO in the murine lung with nuclear imaging using single photon computed tomography (SPECT).
methodsZampilimab was bioconjugated with DOTAGA and radiolabeled with Indium-111, then administered intravenously to nude female mice receiving hTG2-positive cells either subcutaneously (s.c.) or intratracheally (i.t.). In blocking groups, [111In]In-DOTAGA-zampilimab was simultaneously injected with a 100X excess of unlabeled antibody. SPECT imaging was performed for three days following [111In]In-DOTAGA-zampilimab administration.
resultsFor all the timepoints, SPECT imaging revealed a significant uptake of radiolabeled zampilimab in hTG2-positive s.c. tumors. Furthermore, mice receiving exogenous cells i.t. displayed a greater pulmonary uptake of [111In]In-DOTAGA-zampilimab compared to the control group. The binding specificity of zampilimab to hTG2 was confirmed with competition experiments in which the administration of excess unlabeled zampilimab significantly prevented the uptake of the radiolabeled antibody.
conclusionsThe administration of hTG2-positive cells provided a straightforward and cost-effective animal model for evaluating the TO of zampilimab. Results derived from the i.t. administration model consistently confirmed that zampilimab can reach the lung and specifically bind hTG2. Additionally, our study demonstrated that zampilimab can be effectively radiolabeled for SPECT imaging, allowing for a non-invasive and quantitative assessment of lung TO, paving the way to its clinical application.
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