Background: Extracellular Traps (ETs) contribute to the pathophysiology of multiple immune-mediated inflammatory diseases including Rheumatoid Arthritis (RA), and may be promising therapeutic targets. The first-in-class therapeutic anti-citrullinated histone antibody CIT-013 binds citrullinated histones H2A and H4 in ETs and has demonstrated efficacy in models of ET-mediated inflammation by inhibiting de novo ET formation and by enhancing clearance of existing ETs by Fc receptor-mediated phagocytosis (Chirivi et al 2021; van der Linden et al 2023).

Objectives: The objective of this study was to visualize ETs in inflamed tissues using an ET targeting antibody as an in vivo radiotracer.

Methods: Mice with collagen induced arthritic (CIA) mice with no, mild, moderate and established disease (n=10/group) were intravenously injected with indium-111 labeled mouse anti-citrullinated histone antibody (mACHA). Twenty-four hours after injection, whole body Single Photon Emission Computed Tomographic (SPECT) imaging was performed on selected animals. For all animals, tissue distribution of the radiotracer was quantified ex vivo by measuring gamma radiation.

Results: In CIA mice, indium-111 labeled mACHA distributes to inflamed joints and can be detected in animals with mild inflammation with increasing accumulation of the radiotracer in the fore and hind paws correlating with higher arthritis severity. Furthermore, the radiotracer enables a highly sensitive detection of inflammation in joints not apparently inflamed upon visual inspection, such as the knee.

Conclusions: mACHA can be used as a radiotracer to visualize ETs in sites of inflammation. This proof of principle imaging study enabled an ongoing human whole body PET CT imaging clinical study in RA and hidradenitis suppurativa patients. This clinical study will lead to further insights in CIT-013’s distribution, target engagement and mechanism of action in patients with immune mediated inflammatory diseases.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: Annemarie Kip Citryll BV, Eric Meldrum Citryll BV, Birgitte Walgreen: None declared, Helmuth van Es Citryll BV, Citryll BV, Monique Helsen: None declared, Daphne Dorst: None declared, Marije Koenders: None declared, Renato Chirivi Citryll BV, Citryll BV.