ECTS Abstracts (2015) 1 P6

Targeted depletion of resident synovial macrophages in antigen induced arthritis using liposome encapsulated clodronate reduces iron oxide nanoparticle MRI signal in vivo

Azza Gramoun1,4, Lindsey Crowe1, Wolfgang Wirth2, Lionel Maurizi3, Geraldine Coullerez3, Kerstin Grosdemange1, Felix Eckstein2, Heinrich Hofmann3 & Jean-Paul Vallee1

1Division of Radiology, Geneva University Hospitals, Foundation for Medical Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland; 2Institute of Anatomy, Paracelsus Medical University, Salzburg, Austria; 3Powder Technology Laboratory, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; 4Department of Oral Biology, Faculty of Oral and Dental Medicine, Cairo University, Cairo, Egypt.

Encapsulating clodronate in a liposome bilayer (Clod-Lipo) enhances its phagocytosis by macrophages and subsequently its effectiveness in killing the phagocytic cells. In this study, we have employed this technique to compare the effect of eliminating different macrophage/monocyte populations on super paramagnetic iron oxide nanoparticles (SPION) uptake in the knee joint during antigen induced arthritis (AIA). To achieve this goal, rats were injected with Clod-Lipo or its negative control liposome encapsulated PBS (PBS-Lipo) twice before AIA induction either intraperitoneally (i.p.); targeting the spleen macrophages, intravenously (i.v.); targeting mostly monocytes but also reticulocytes in the liver and spleen or intra-articularly (i.a.); targeting synovial macrophages. Five days after AIA induction, the rats received 2.5 mg SPION via i.v. injection. The SPION signal was monitored using VIBE MR sequence on days 6 and 10. The 3D MR signal was quantified using a new segmentation software. At the end of MR scanning, the knee joints were dissected, sectioned and analyzed to confirm the MR results. Comparing the effect of the different injection routes on the SPION signal in the knee joint revealed that only the i.a. injection of Clod-Lipo was effective in reducing that signal on day 6 which almost disappeared by day 10. Injecting Clod-Lipo through the i.v. and i.p. routes had no or little effect on that SPION signal. We also noted a significant decline in intra-articular oedema in the the i.a. Clod-Lipo group. The histological assessment on Prussian blue stained sections depicting SPION clusters also confirmed the MR results where a 65% decrease in the number and area of Prussian blue particles was found between the Clod-Lipo group and the non-treated group and PBS-Lipo groups.

Disclosure: The authors declared no competing interests. The research leading to these results has received funding from the European Union Seventh Framework Programme NMP-2008-4.0-1, GRANT AGREEMENT No 228929 (Project NanoDiaRA).