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Evaluation of Tc-rhAnnexin V-128 SPECT/CT as a diagnostic tool for early stages of interstitial lung disease associated with systemic sclerosis


Schniering, Janine; Guo, Li; Brunner, Matthias; Schibli, Roger; Ye, Shuang; Distler, Oliver; Béhé, Martin; Maurer, Britta (2018). Evaluation of Tc-rhAnnexin V-128 SPECT/CT as a diagnostic tool for early stages of interstitial lung disease associated with systemic sclerosis. Arthritis Research & Therapy, 20(1):183.

Abstract

BACKGROUND
Given the need for early detection of organ involvement in systemic sclerosis, we evaluated Tc-rhAnnexin V-128 for the detection of early stages of interstitial lung disease (ILD) in respective animal models using single photon emission computed tomography (SPECT/CT).
METHODS
In bleomycin (BLM)-challenged mice, fos-related antigen 2 (Fra-2) transgenic (tg) mice and respective controls, lung injury was evaluated by analysis of hematoxylin and eosin (HE) and Sirius red staining, with semi-quantification of fibrosis by the Ashcroft score. Apoptotic cells were identified by TUNEL assay, cleaved caspase 3 staining and double staining with specific cell markers. To detect early stages of lung remodeling by visualization of apoptosis, mice were injected intravenously with Tc-rhAnnexin V-128 and imaged by small animal SPECT/CT. For confirmation, biodistribution and ex vivo autoradiography studies were performed.
RESULTS
In BLM-induced lung fibrosis, inflammatory infiltrates occurred as early as day 3 with peak at day 7, whereas pulmonary fibrosis developed from day 7 and was most pronounced at day 21. In accordance, the number of apoptotic cells was highest at day 3 compared with saline controls and then decreased over time. Epithelial cells (E-cadherin+) and inflammatory cells (CD45+) were the primary cells undergoing apoptosis in the earliest remodeling stages of experimental ILD. This was also true in the pathophysiologically different Fra-2 tg mice, where apoptosis of CD45+ cells occurred in the inflammatory stage. In accordance with the findings on tissue level, at day 3 in the BLM and at week 16 in the Fra-2 tg model, biodistribution and/or ex vivo autoradiography showed increased pulmonary uptake of Tc-rhAnnexin V-128 compared with controls. However, accumulation of the radiotracer and thus the signal intensity in lungs was too low to allow the differentiation of healthy and injured lungs in vivo.
CONCLUSION
At the tissue level, Tc-rhAnnexin V-128 successfully demonstrated early stages of ILD in two animal models by detection of apoptotic epithelial and/or inflammatory cells. In vivo, however, we did not detect early lung injury. It remains to be investigated whether the same applies to human ILD.

Abstract

BACKGROUND
Given the need for early detection of organ involvement in systemic sclerosis, we evaluated Tc-rhAnnexin V-128 for the detection of early stages of interstitial lung disease (ILD) in respective animal models using single photon emission computed tomography (SPECT/CT).
METHODS
In bleomycin (BLM)-challenged mice, fos-related antigen 2 (Fra-2) transgenic (tg) mice and respective controls, lung injury was evaluated by analysis of hematoxylin and eosin (HE) and Sirius red staining, with semi-quantification of fibrosis by the Ashcroft score. Apoptotic cells were identified by TUNEL assay, cleaved caspase 3 staining and double staining with specific cell markers. To detect early stages of lung remodeling by visualization of apoptosis, mice were injected intravenously with Tc-rhAnnexin V-128 and imaged by small animal SPECT/CT. For confirmation, biodistribution and ex vivo autoradiography studies were performed.
RESULTS
In BLM-induced lung fibrosis, inflammatory infiltrates occurred as early as day 3 with peak at day 7, whereas pulmonary fibrosis developed from day 7 and was most pronounced at day 21. In accordance, the number of apoptotic cells was highest at day 3 compared with saline controls and then decreased over time. Epithelial cells (E-cadherin+) and inflammatory cells (CD45+) were the primary cells undergoing apoptosis in the earliest remodeling stages of experimental ILD. This was also true in the pathophysiologically different Fra-2 tg mice, where apoptosis of CD45+ cells occurred in the inflammatory stage. In accordance with the findings on tissue level, at day 3 in the BLM and at week 16 in the Fra-2 tg model, biodistribution and/or ex vivo autoradiography showed increased pulmonary uptake of Tc-rhAnnexin V-128 compared with controls. However, accumulation of the radiotracer and thus the signal intensity in lungs was too low to allow the differentiation of healthy and injured lungs in vivo.
CONCLUSION
At the tissue level, Tc-rhAnnexin V-128 successfully demonstrated early stages of ILD in two animal models by detection of apoptotic epithelial and/or inflammatory cells. In vivo, however, we did not detect early lung injury. It remains to be investigated whether the same applies to human ILD.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Rheumatology
Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:16 August 2018
Deposited On:24 Aug 2018 11:57
Last Modified:08 Apr 2020 23:53
Publisher:BioMed Central
ISSN:1478-6354
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/s13075-018-1681-1
PubMed ID:30115119

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