Preclinical evaluation of a radioiodinated fully human antibody for in vivo imaging of vascular adhesion protein-1-positive vasculature in inflammation

• Published in: Journal of Nuclear Medicine Vol. 54; no. 8; pp. 1315 - 1319
• Main Authors: Autio, Anu, Vainio, Petri J, Suilamo, Sami, Mali, Antti, Vainio, Jani, Saanijoki, Tiina, Noponen, Tommi, Ahtinen, Helena, Luoto, Pauliina, Teräs, Mika, Jalkanen, Sirpa, Roivainen, Anne
• Format: Journal Article
• Language: English
• Published: United States Society of Nuclear Medicine 01.08.2013
• Subjects: Amine Oxidase (Copper-Containing) - immunology; Amine Oxidase (Copper-Containing) - metabolism; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacokinetics; Cell adhesion & migration; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Humans; Inflammation - diagnostic imaging; Inflammation - metabolism; Inflammation - physiopathology; Iodine Radioisotopes; Medical imaging; Molecular Imaging - methods; Monoclonal antibodies; Multimodal Imaging; Neovascularization, Pathologic - diagnostic imaging; Nuclear medicine; Positron-Emission Tomography; Proteins; Rabbits; Radiation Dosage; Radioactivity; Tomography, X-Ray Computed; radioiodination; antibody; nuclear imaging; vascular adhesion protein-1; rabbit
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.113.120295

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. 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 (124)I-BTT-1023 were extrapolated. Additionally, rabbits with chemically induced synovitis were imaged with (123)I-BTT-1023 SPECT/CT. 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 (124)I-BTT-1023 was 0.55 mSv/MBq, if blockage of thyroid uptake is assumed. The radioiodinated BTT-1023 was able to detect mild inflammation in vivo. Clinical (124)I-BTT-1023 PET studies with injected radioactivity of 0.5-0.7 MBq/kg may be justified.