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EJNMMI Res. 2019 Sep 9;9(1):87. doi: 10.1186/s13550-019-0541-6.

In vivo imaging of early stages of rheumatoid arthritis by α5β1-integrin-targeted positron emission tomography.

Author information

1
Institute of Pathology, Technische Universität München, Trogerstr. 18, 81675, Munich, Germany. johannes.notni@tum.de.
2
Department of Diagnostic and Interventional Radiology, Technische Universität München, Munich, Germany.
3
Institute of Pathology, Technische Universität München, Trogerstr. 18, 81675, Munich, Germany.
4
German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.
5
Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
6
Institute for Advanced Study, Department of Chemistry, Technische Universität München, Garching, Germany.

Abstract

BACKGROUND:

Rheumatoid arthritis (RA) is one of the most common rheumatic diseases. Joint inflammation and pathological growth of joint cartilage cause swollen and painful joints, which severely diminishes the patients' life quality. There is no causal treatment. Symptomatic therapies should start as early as possible to take maximal effect. Hence, diagnostic procedures capable of detecting affected joints before the onset of clinical symptoms are highly desirable. We explored the value of PET imaging of integrin subtypes αvβ3 and α5β1 for early detection of RA foci in collagen-induced arthritis (CIA) mouse models.

RESULTS:

Development of RA in CIA mice was monitored by paw scoring, and αvβ3- and α5β1-integrin expression was quantified by μPET using 68Ga-Avebetrin and 68Ga-Aquibeprin. For consecutive sections of selected decalcified joints (knee, ankle), arthritic degeneration and integrin expression were assessed by MOVAT staining and β3/α5 immunohistochemistry (IHC), respectively. β3- and α5-IHC revealed elevated levels of both αvβ3- and α5β1-integrin in arthritic joints. Unlike αvβ3, α5β1 is strongly expressed in the proliferating synovial lining layer, which suggests that its presence is directly related to RA development. For mice with advanced RA (6 weeks after CIA), PET signals for α5β1-integrin were substantially stronger (> 300% of baseline) than that of αvβ3-integrin (< 200%). A longitudinal PET follow-up revealed that the manifestation of clinical symptoms of RA is preceded by upregulation of α5β1- but not of αvβ3-integrin.

CONCLUSION:

α5β1-integrin PET could add a new functional imaging aspect to the portfolio of RA diagnostics because it appears to be a sensitive biomarker for early RA development. We suggest α5β1-integrin PET as a valuable tool to achieve a higher precision for early diagnosis of RA, including initial staging, monitoring of the disease course, and drug treatment, and for planning of radiosynoviorthesis (RSO).

KEYWORDS:

Animal models; Collagen-induced arthritis; Immunohistochemistry; Integrins; Positron emission tomography; Rheumatoid arthritis

PMID:
31501931
DOI:
10.1186/s13550-019-0541-6

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