A novel model for the pre-clinical imaging of inflamed human synovial vasculature.
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 (111)In-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 (111)In-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.
Garrood
Toby
T
William Harvey Research Institute, Barts and the London School of Medicine, Charterhouse Square, London, UK.
Blades
Mark
M
Haskard
Dorian O
DO
Mather
Stephen
S
Pitzalis
Costantino
C
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D019040:E-Selectin / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007205:Indium Radioisotopes; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D010003:Osteoarthritis / Q000276:immunology*; D004369:Pentetic Acid / Q000276:immunology; D019275:Radiopharmaceuticals; D013583:Synovial Membrane / Q000098:blood supply* / Q000637:transplantation; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014183:Transplantation, Heterologous
D001323:Autoantibodies; D019040:E-Selectin; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D004369:Pentetic Acid