EANM recommendations based on systematic analysis of small animal radionuclide imaging in inflammatory musculoskeletal diseases

Abstract

Inflammatory musculoskeletal diseases represent a group of chronic and disabling conditions that evolve from a complex interplay between genetic and environmental factors that cause perturbations in innate and adaptive immune responses. Understanding the pathogenesis of inflammatory musculoskeletal diseases is, to a large extent, derived from preclinical and basic research experiments. In vivo molecular imaging enables us to study molecular targets and to measure biochemical processes non-invasively and longitudinally, providing information on disease processes and potential therapeutic strategies, e.g. efficacy of novel therapeutic interventions, which is of complementary value next to ex vivo (post mortem) histopathological analysis and molecular assays. Remarkably, the large body of preclinical imaging studies in inflammatory musculoskeletal disease is in contrast with the limited reports on molecular imaging in clinical practice and clinical guidelines. Therefore, in this EANM-endorsed position paper, we performed a systematic review of the preclinical studies in inflammatory musculoskeletal diseases that involve radionuclide imaging, with a detailed description of the animal models used. From these reflections, we provide recommendations on what future studies in this field should encompass to facilitate a greater impact of radionuclide imaging techniques on the translation to clinical settings.

Positron Emission Tomography-Computed Tomography and Magnetic Resonance Imaging Assessments in a Mouse Model of Implant-Related Bone and Joint Staphylococcus aureus Infection

“…In addition, neither technique can always differentiate between infection and sterile inflammation. Nevertheless, animal models of bacterial bone infection have proved to be essential in translational research ( 13 , 19 ). In the present study, we used a radiolucent resorbable material to create a focus of infection that mimicked osteomyelitis.…”

“…Finally, nuclear imaging was the only modality that enabled the acquisition of quantitative data. However, many studies of small animal imaging for inflammatory musculoskeletal conditions lack quantitative analysis ( 13 ). This feature constituted an advantage, because it enabled more objective, sensitive statistical assessments than purely structural techniques.…”

“…Animal models can be useful, and many mouse models have gained importance ( 11 , 12 ) in preclinical settings. However, the sensitivity of structural imaging techniques depends heavily on the animal model ( 13 ). Horst et al ( 14 ) showed that MRI and CT could reveal bone structure changes during the chronic stage (i.e., 1 month after bacterial inoculation) of hematogenous osteomyelitis caused by S. aureus in a mouse model.…”

The Development and Validation of Radiopharmaceuticals Targeting Bacterial Infection

“…When choosing an animal model, it is important to thoroughly understand the human infection that is being studied, as well as the strengths and limitations of a given model. The European Association of Nuclear Medicine recently published useful guidelines for choosing the appropriate animal model for preclinical experiments (53). In most cases, the models used should recapitulate human pathologies.…”

Editorial: Nuclear medicine in rheumatological diseases' therapy and diagnosis

“…Furthermore, radiopharmaceuticals may be used as therapeutic options in patients with rheumatological diseases. The application of nuclear medicine techniques in the diagnosis and management of rheumatological diseases relies on the detection of in vivo functional abnormalities at an early stage of the diseases, earlier compared to the structural changes detected by conventional imaging (1)(2)(3)(4)(5)(6)(7).…”