Anning Li MD, Presenter: Nothing to Disclose

Yue Wu, Abstract Co-Author: Nothing to Disclose

Cuihua Wang PhD, Abstract Co-Author: Nothing to Disclose

Benjamin Pulli MD, Abstract Co-Author: Nothing to Disclose

Gregory R. Wojtkiewicz MSc, Abstract Co-Author: Nothing to Disclose

Yoshiko Iwamoto, Abstract Co-Author: Nothing to Disclose

Muhammad Ali MBBS, Abstract Co-Author: Nothing to Disclose

JINGHUI LI PHD, Abstract Co-Author: Nothing to Disclose

Zhenwei Yao, Abstract Co-Author: Nothing to Disclose

John Chen MD, PhD, Abstract Co-Author: Research Grant, Pfizer Inc

Purpose: Glatiramer acetate (GA), a first-line drug for multiple sclerosis (MS), is thought to primarily increase Th2 anti-inflammatory lymphocytes while 4-animobenzoic acid hydrazide (ABAH) is an irreversible inhibitor for myeloperoxidase (MPO), a major product of pro-inflammatory myeloid cells. The aim of this study was to investigate whether the combination of these two agents could be more beneficial, and whether this benefit could be evaluated and tracked by molecular imaging targeting MPO.

Materials and Methods: 3 groups of experimental autoimmune encephalomyelitis (EAE) mice were given sub-optimal doses: ABAH 20mg/kg bid, GA 75μg qd, combination (ABAH 20mg/kg bid and GA 75μg qd) and saline as control. Mice were imaged when they first became symptomatic with bis-5HT-DTPA-Gd (MPO-Gd) MRI to assess MPO activity in vivo. Analysis of lesion number, lesion size and contrast-to-noise ratios (CNRs) was conducted. Histopathology was used to analyze the disease activity. Statistical analysis was performed using Student’s t-test with P<0.05 as significant.

Results: The combination group showed delayed disease onset, reduced disease severity (Fig. A) and significantly less disease burden (Fig. B) compared to the ABAH group (P<0.005) and GA group (P<0.05). The combined treatment also tended to improve survival (Fig. A). On imaging, the combination group showed fewer lesions (51.0±11.2 for combination vs. 100.8±11.9 for ABAH, P<0.01; vs. 87.3±14.6 for GA, P<0.05), smaller lesion size (23.9±4.5 for combination vs. 73.0±26.5 for ABAH, P<0.05; vs. 90.1±36.5 for GA, P<0.05) and lower image intensity (2.7±0.6 for combination vs. 6.8±1.3 for ABAH, P<0.01; vs. 4.6±0.7 for GA, P<0.05). Reduced disease severity was confirmed on histopathology, where inflammatory cells infiltration, MPO expression, and demyelination were attenuated (Fig. C).

Conclusion: Molecular MR imaging targeting MPO can track the beneficial effect of synergistic treatment effects of targeting lymphoid and myeloid inflammation, establishing MPO imaging as a potential imaging biomarker for MS.

Clinical Relevance: Upon translation, MPO targeted MR imaging could be used to track MS treatment efficiency and guide treatment decisions.

Li, A, Wu, Y, Wang, C, Pulli, B, Wojtkiewicz, G, Iwamoto, Y, Ali, M, LI, J, Yao, Z, Chen, J, Molecular MRI Detects Synergistic Combination of Glatiramer Acetate and Myeloperoxidase Inhibition in a Mouse Model of Multiple Sclerosis.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14011056.html