Henry Su MD, PhD, Presenter: Nothing to Disclose

John Chen MD, PhD, Abstract Co-Author: Nothing to Disclose

Elena Aikawa MD, PhD, Abstract Co-Author: Nothing to Disclose

Michael Breckwoldt, Abstract Co-Author: Nothing to Disclose

Matthias Nahrendorf, Abstract Co-Author: Nothing to Disclose

Ralph Weissleder MD, PhD, Abstract Co-Author: Board of Directors, VisEn Medical, Inc

To assess whether an activatable MR contrast agent targeting myeloperoxidase (MPO), an enzyme secreted by inflammatory cells, can noninvasively confirm vasculitis in a mouse model of Kawasaki disease.

MPO-sensitive agent bis-5HT-DTPA(Gd) was synthesized by the CMIR Chemistry Core. MCLS-2 strain of Candida albicans was cultured and protein subsequently purified for intraperitoneal injection into six 4-week old C57BL6. C57BL6 mice with saline injections were used as controls. 8 weeks after induction, MR imaging of the aortic root was performed using a 7T Bruker Pharmascan MRI scanner, before and after intravenous injection of either 0.3 mmol/kg of DTPA(Gd) as control or 0.3 mmol/kg of bis-5HT-DTPA(Gd). Following imaging, animals were sacrificed and aortic roots processed for immunohistochemistry assaying for MPO, neutrophils, and macrophages.

In the presence of MPO, bis-5HT-DTPA(Gd) oligomerizes and binds to proteins, causing increased T1-weighted signal and retention of the agent at sites of increased MPO activity. In mice injected with the protein extract, there was increased thickening of the aortic roots on T1 pre-contrast images, but not in control mice. MPO targeted imaging showed increased enhancement at these inflamed sites at the aortic root. At 90 min., enhancement with DTPA(Gd) imaging nearly returned to baseline while MPO imaging retained more than 80% of peak enhancement (p<0.5), consistent with agent activation and the presence of inflammation. Immunohistochemical studies confirmed MPO presence in the aortic root, which also corresponded to diffuse inflammatory cell infiltration.

MPO-targeted molecular imaging can noninvasively confirm vascular inflammation in a mouse model.

Currently, diagnosing vasculitis can only be made with invasive biopsy. MPO-targeted molecular imaging has the potential to noninvasively confirm vasculitis in suspected patients and improve disease.

Su, H, Chen, J, Aikawa, E, Breckwoldt, M, Nahrendorf, M, Weissleder, R, Noninvasive in Vivo Imaging of Vasculitis by Targeting the Inflammatory Enzyme Myeloperoxidase.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5009903.html