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Abstract Number: 3177

Targeted Nuclear Imaging for the Early Detection of Lung Involvement in Systemic Sclerosis

Janine Schniering1, Stephanie Haller2, Zhongning Guo1, Martina Benesova2,3, Carol A. Feghali-Bostwick4, Roger Schibli2,3, Oliver Distler5, Cristina Müller2,3 and Britta Maurer5, 1Department of Rheumatology, University Hospital Zurich, Schlieren, Switzerland, 2Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen PSI, Switzerland, 3Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zurich, Switzerland, 4Medicine, Medical University of South Carolina, Charleston, SC, 5Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: fibrosis, Imaging, inflammation and interstitial lung disease

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Session Information

Date: Wednesday, November 16, 2016

Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Pathogenesis, Animal Models and Genetics II

Session Type: ACR Concurrent Abstract Session

Session Time: 9:00AM-10:30AM

Background/Purpose: Interstitial lung disease (ILD) is one of the main causes of systemic sclerosis (SSc)-related deaths. Since routine diagnostics such as high resolution computed tomography and pulmonary function tests often only detect ILD at disease stages with already impaired organ function and/or damage, there is an unmet clinical need for the non-invasive diagnosis of ILD at earliest, still reversible stages.  Here, we assessed new radiotracers for the detection of SSc-ILD specifically targeting integrin αvβ3 and folate receptor β (FR-β) as molecular players of inflammation and inflammation-dependent fibrosis in the murine model of bleomycin-induced lung fibrosis.

Methods: Expression of integrin αvβ3 and FR-β was analyzed in lung sections from patients with SSc-ILD, idiopathic pulmonary fibrosis (IPF) (n=5-6), healthy controls (n=4-5) as well as from bleomycin-treated mice and respective controls (n=6) using immunohistochemistry. In vivo imaging was performed using a RGD peptide derivative and a folate derivative radiolabeled with the gamma-radiation emitting radionuclide Lutetium-177 (177Lu). SPECT (single photon emission computed tomography) was performed using a dedicated small-animal SPECT/CT scanner. Animals were scanned at day 7 after intratracheal installation of bleomycin to visualize pulmonary inflammation and incipient fibrosis. The specific pulmonary accumulation of the radiotracer was confirmed by ex vivo SPECT/CT, biodistribution, and autoradiography studies.

Results: In lung sections of patients with SSc-ILD and IPF, the expression of integrin αvβ3 was significantly increased compared to healthy controls (p<0.009, p<0.02). In contrast, FR-β expression was only significantly upregulated in lungs from SSc-ILD (p<0.04), but not in IPF patients. In line with the results obtained in SSc-ILD, lungs of bleomycin-treated mice, but not of controls showed a significant increase in integrin αvβ3 expression and FR-β expression (p<0.03. p<0.05, Fig. C). Notably, at day 7 after intratracheal installation of bleomycin, SPECT/CT with 177Lu-RGD targeting integrin αvβ3, successfully visualized pulmonary inflammation and incipient fibrosis in the model of bleomycin-induced lung fibrosis. Similarly, SPECT/CT of FR-β showed a higher pulmonary uptake of the 177Lu-folate radiotracer in bleomycin-treated mice than in controls (Fig. A). Ex vivo SPECT/CT, biodistribution and autoradiography studies confirmed the in vivo results and validated the specific uptake of both radiotracers in lungs from bleomycin-challenged mice as compared to controls (Fig. B).

Conclusion: The here presented data provide evidence that targeting molecular players of inflammation and inflammation-dependent fibrosis using nuclear imaging methods may lead to a novel promising non-invasive approach for the early detection of lung involvement in SSc.

   


Disclosure: J. Schniering, None; S. Haller, None; Z. Guo, None; M. Benesova, None; C. A. Feghali-Bostwick, None; R. Schibli, None; O. Distler, Bayer, Sanofi, Ergonex, Boehringer Ingelheim, Actelion, Pfizer, 2,4 D Science, Actelion, Active Biotec, Bayer, BiogenIdec, BMS, Boehringer Ingelheim, EpiPharm, Ergonex, espeRare foundation, Genentech/Roche, GSK, Inventiva, Lilly, medac, MedImmune, Pharmacyclics, Pfizer, Serodapharm, Sinoxa, 5; C. Müller, None; B. Maurer, AbbVie, Protagen, EMDO, 2, 9,Roche, Actelion, 9.

To cite this abstract in AMA style:

Schniering J, Haller S, Guo Z, Benesova M, Feghali-Bostwick CA, Schibli R, Distler O, Müller C, Maurer B. Targeted Nuclear Imaging for the Early Detection of Lung Involvement in Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/targeted-nuclear-imaging-for-the-early-detection-of-lung-involvement-in-systemic-sclerosis/. Accessed February 2, 2023.
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