Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

Abstract

The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-α, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with 99mTc or 111In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform ‘evidence-based biological therapy’ of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and follow-up.

A Molecular Imaging Primer: Modalities, Imaging Agents, and Applications

“…Unlike small molecules and peptides, mAbs are not restricted to interacting with binding pockets or active sites, but instead can bind adhesion molecules, activation markers, antigens, and receptors (270). Their relatively facile synthesis and unparalleled ability to recognize and bind their target site with ultra high affinity and specificity have made mAbs (and their engineered fragments) important players in the therapeutic and diagnostic arenas (448).…”

The molecular imaging approach to image infections and inflammation by nuclear medicine techniques

“…Published results showed that RA patients with painful joints but negative (low target-to-background ratio) at pre-therapy scintigraphy do not benefit from unlabeled anti-TNFa therapy, whereas patients with positive (high tumor-tobackground ratio) at pre-therapy scintigraphy in joints showed most clinical benefit from therapy [107].…”

Nuclear Medicine in Musculoskeletal Disorders: Clinical Approach

“…It can affect many organ systems and it is also associated with a higher prevalence of other diseases such as infections, neoplasms and cardiovascular disease. It has been shown that 50% of patients with RA are disabled within 10 years of onset of disease and survival is reduced (Malviya et al, 2010;as cited in Solomon et al, 2003, Wolfe et al, 1994. Conventional radiology is the most wide-spread technique for the appraisal of RA, since it allows the evaluation of the presence or absence of erosions, joint space narrowing or articular osteopenia, but only when symptoms have been present for several months or years.…”

“…64Cu-labelled anti-GPI, 68Ga-labelled annexin V or 123I-antileukoproteinase) are being identified as therapeutic targets and used to develop new radiopharmaceuticals which accumulate in areas of inflammation where they can be located and quantified. Their study and description will allow improving the understanding of the complex pathophysiology of RA and detecting changes in very early stages of this disease and will give us the possibility of a pre-therapy scintigraphic approach with radiolabelled monoclonal antibodies that will let us evaluate the presence of target molecules in the inflammatory lesion, thus helping in the selection of the most efficient therapy and predicting therapy response (Glaudemans et al, 2010;Malviya et al, 2010). But currently, these techniques are not used in clinical practice and remain like a research tool inside selected laboratories.…”