Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple different organs, including the kidneys and central nervous system (CNS). Conventional radiological examinations in SLE patients include volumetric/ anatomical computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US). The utility of these modalities is limited, however, due to the complexity of the disease. Furthermore, CT and MRI contrast agents are contraindicated in patients with renal impairment. Various radiologic methods are currently being developed to improve disease characterization in patients with SLE beyond simple anatomical endpoints. Physiological non-contrast MRI protocols have been developed to assess tissue oxygenation, glomerular filtration, renal perfusion, interstitial diffusion, and inflammation-driven fibrosis in lupus nephritis (LN) patients. For neurological symptoms, vessel size imaging (VSI, an MRI approach utilizing T2-relaxing iron oxide nanoparticles) has shown promise as a diagnostic tool. Molecular imaging probes (mostly for MRI and nuclear medicine imaging) have also been developed for diagnosing SLE with high sensitivity, and for monitoring disease activity. This paper reviews the challenges in evaluating disease activity in patients with LN and neuropsychiatric systemic lupus erythematosus (NPSLE). We describe novel MRI and positron-emission tomography (PET) molecular imaging protocols using targeted iron oxide nanoparticles and radioactive ligands, respectively, for detection of SLE-associated inflammation.
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any organ throughout the body[1]
The treatment of SLE almost always employs immunomodulatory therapies that suppress this autoimmune response. Immunosuppressive drugs, such as cyclophosphamide and mycophenolate mofetil (MMF), reduce tissue inflammation and injury, and the mortality for patients with SLE has improved in recent decades[2,3]
The T2 signal did not decrease in age-matched MRL/lpr mice injected with untargeted superparamagnetic iron-oxide nanoparticles (SPIONs), nor in healthy control mice injected with complement receptor-2 (CR2)-targeted SPIONs. These results indicate that the CR2-targeted SPIONs can be used to non-invasively detect active glomerulonephritis by T2-magnetic resonance imaging (MRI) based on tissue-bound C3-complement activation
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect any organ throughout the body[1]. These results indicate that the CR2-targeted SPIONs can be used to non-invasively detect active glomerulonephritis by T2-MRI based on tissue-bound C3-complement activation To determine whether this method can be used to assess disease severity, we repeated the protocol at four week intervals in MRL/lpr mice[80]. PET probes can be detected with higher sensitivity than SPIONs (Figure 1), and we have developed high-affinity anti-C3d monoclonal antibodies that accumulate at sites of complement activation after systemic injection[81]. A high degree of signal was seen in the kidneys of fH-/- mice and MRL/lpr mice after injection with the antibody (unpublished data) These pilot experiments confirm that radiolabeled C3 probes can detect glomerular C3 fragments in mice with lupus-like glomerulonephritis.
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