Preclinical Evaluation of a Radioiodinated Fully Human Antibody for In Vivo Imaging of Vascular Adhesion Protein-1–Positive Vasculature in Inflammation

Vascular adhesion protein-1 (VAP-1) is an endothelial glycoprotein mediating leukocyte trafficking from blood to sites of inflammation. BTT-1023 is a fully human monoclonal anti-VAP-1 antibody developed to treat inflammatory diseases. In this study, we preclinically evaluated radioiodinated BTT-1023 for inflammation imaging. Methods: Rabbits were intravenously injected with radioiodinated BTT-1023. Distribution and pharmacokinetics were assessed by PET/CT up to 72 h after injection. Human radiation dose estimates for 124I-BTT-1023 were extrapolated. Additionally, rabbits with chemically induced synovitis were imaged with 123I-BTT-1023 SPECT/CT. Results: Radioiodinated BTT-1023 cleared rapidly from blood circulation and distributed to liver and thyroid. Inflamed joints were delineated by SPECT/CT. The estimated human effective dose due to 124I-BTT-1023 was 0.55 mSv/MBq, if blockage of thyroid uptake is assumed. Conclusion: The radioiodinated BTT-1023 was able to detect mild inflammation in vivo. Clinical 124I-BTT-1023 PET studies with injected radioactivity of 0.5–0.7 MBq/kg may be justified.