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Rheumatology Advance Access originally published online on June 2, 2009
Rheumatology 2009 48(8):926-931; doi:10.1093/rheumatology/kep117
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A novel model for the pre-clinical imaging of inflamed human synovial vasculature

Toby Garrood1, Mark Blades1, Dorian O. Haskard2, Stephen Mather3 and Costantino Pitzalis1

1William Harvey Research Institute, Barts and the London School of Medicine, 2Eric Bywaters Centre, Imperial College London and 3Centre for Cancer Imaging, Queen Mary University of London, London, UK.

Correspondence to: Costantino Pitzalis, William Harvey Research Institute, Barts and the London School of Medicine, Charterhouse Square, London EC1M 6BQ, UK. E-mail: c.pitzalis{at}qmul.ac.uk


  Abstract

Objective. The purpose of this study was to explore the development of a pre-clinical nuclear imaging model as a tool for testing novel radiopharmaceutical agents for imaging and/or delivery systems to human tissues. Here we report for the first time the imaging of human synovial tissue transplanted into SCID mice using a radiolabelled anti-E-selectin antibody and NanoSPECT/CT technology.

Methods. Human synovium was transplanted into SCID mice. Two to three weeks post-transplantation tissue vasculature was stimulated with TNF-{alpha} by intra-graft injection 5 h prior to intravenous injection of 111In-labelled anti-E-selectin or isotype control antibody. At 1, 4, 24 and 48 h animals were imaged and transplant activity quantified.

Results. Activity was detectable in the grafts at all time points, with clear delineation of the transplants in the reconstructed images. A significant difference in graft radioactivity was observed at 4 and 24 h with a significantly higher uptake (P < 0.05) of 111In-anti-E-selectin compared with isotype control antibody.

Conclusions. This article highlights NanoSPECT/CT imaging in the SCID mouse chimeric model as a powerful tool for the pre-clinical development of radiopharmaceutical and delivery agents targeting human synovial tissue in vivo.

KEY WORDS: Rheumatoid arthritis, Radionuclide imaging, Synovium, E-selectin, SPECT, Imaging, Antibody, Animal, Transplantation, Tumour necrosis factor-{alpha}

Submitted 18 November 2008; revised version accepted 14 April 2009.
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