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

J Nucl Med. 2013 Aug;54(8):1315-9. doi: 10.2967/jnumed.113.120295. Epub 2013 Jul 11.

Abstract

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 (124)I-BTT-1023 were extrapolated. Additionally, rabbits with chemically induced synovitis were imaged with (123)I-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 (124)I-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 (124)I-BTT-1023 PET studies with injected radioactivity of 0.5-0.7 MBq/kg may be justified.

Keywords: antibody; nuclear imaging; rabbit; radioiodination; vascular adhesion protein-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amine Oxidase (Copper-Containing) / immunology
  • Amine Oxidase (Copper-Containing) / metabolism*
  • Animals
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Monoclonal* / pharmacokinetics
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism*
  • Humans
  • Inflammation / diagnostic imaging
  • Inflammation / metabolism
  • Inflammation / physiopathology
  • Iodine Radioisotopes
  • Molecular Imaging / methods*
  • Multimodal Imaging
  • Neovascularization, Pathologic / diagnostic imaging*
  • Positron-Emission Tomography
  • Rabbits
  • Radiation Dosage
  • Tomography, X-Ray Computed

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Iodine Radioisotopes
  • AOC3 protein, human
  • Amine Oxidase (Copper-Containing)