5 results on '"Cohrs, Susan"'
Search Results
2. 18F-AzaFol for Detection of Folate Receptor-β Positive Macrophages in Experimental Interstitial Lung Disease-A Proof-of-Concept Study
- Author
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Schniering, Janine, Benešová, Martina, Brunner, Matthias, Haller, Stephanie, Cohrs, Susan, Frauenfelder, Thomas, Vrugt, Bart, Feghali-Bostwick, Carol, Schibli, Roger, Distler, Oliver, Müller, Cristina, Maurer, Britta, University of Zurich, and Maurer, Britta
- Subjects
interstitial lung disease ,2403 Immunology ,positron emission tomography ,10042 Clinic for Diagnostic and Interventional Radiology ,Immunology ,10051 Rheumatology Clinic and Institute of Physical Medicine ,610 Medicine & health ,respiratory system ,folate-based 18F-PET tracer ,respiratory tract diseases ,macrophages ,folate receptor ,inflammation ,animal model of lung fibrosis ,10049 Institute of Pathology and Molecular Pathology ,2723 Immunology and Allergy ,imaging biomarkers ,Original Research - Abstract
Background: Interstitial lung disease (ILD) is a common and severe complication in rheumatic diseases. Folate receptor-β is expressed on activated, but not resting macrophages which play a key role in dysregulated tissue repair including ILD. We therefore aimed to pre-clinically evaluate the potential of 18F-AzaFol-based PET/CT (positron emission computed tomography/computed tomography) for the specific detection of macrophage-driven pathophysiologic processes in experimental ILD. Methods: The pulmonary expression of folate receptor-β was analyzed in patients with different subtypes of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. PET/CT was performed at days 3, 7, and 14 after BLM instillation using the 18F-based folate radiotracer 18F-AzaFol. The specific pulmonary accumulation of the radiotracer was assessed by ex vivo PET/CT scans and quantified by ex vivo biodistribution studies. Results: Folate receptor-β expression was 3- to 4-fold increased in patients with fibrotic ILD, including idiopathic pulmonary fibrosis and connective tissue disease-related ILD, and significantly correlated with the degree of lung remodeling. A similar increase in the expression of folate receptor-β was observed in experimental lung fibrosis, where it also correlated with disease extent. In the mouse model of BLM-induced ILD, pulmonary accumulation of 18F-AzaFol reflected macrophage-related disease development with good correlation of folate receptor-β positivity with radiotracer uptake. In the ex vivo imaging and biodistribution studies, the maximum lung accumulation was observed at day 7 with a mean accumulation of 1.01 ± 0.30% injected activity/lung in BLM-treated vs. control animals (0.31 ± 0.06% % injected activity/lung; p < 0.01). Conclusion: Our preclinical proof-of-concept study demonstrated the potential of 18F-AzaFol as a novel imaging tool for the visualization of macrophage-driven fibrotic lung diseases.
- Published
- 2019
3. F-18-AzaFol for Detection of Folate Receptor-beta Positive Macrophages in Experimental Interstitial Lung Disease-A Proof-of-Concept Study
- Author
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Schniering, Janine, Benešová, Martina, Brunner, Matthias, Haller, Stephanie, Cohrs, Susan, Frauenfelder, Thomas, Vrugt, Bart, Feghali-Bostwick, Carol, Schibli, Roger, Distler, Oliver, Müller, Cristina, and Maurer, Britta
- Subjects
interstitial lung disease ,folate receptor ,positron emission tomography ,inflammation ,animal model of lung fibrosis ,imaging biomarkers ,macrophages ,folate-based 18F-PET tracer ,respiratory system ,respiratory tract diseases - Abstract
Background: Interstitial lung disease (ILD) is a common and severe complication in rheumatic diseases. Folate receptor-β is expressed on activated, but not resting macrophages which play a key role in dysregulated tissue repair including ILD. We therefore aimed to pre-clinically evaluate the potential of 18F-AzaFol-based PET/CT (positron emission computed tomography/computed tomography) for the specific detection of macrophage-driven pathophysiologic processes in experimental ILD. Methods: The pulmonary expression of folate receptor-β was analyzed in patients with different subtypes of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. PET/CT was performed at days 3, 7, and 14 after BLM instillation using the 18F-based folate radiotracer 18F-AzaFol. The specific pulmonary accumulation of the radiotracer was assessed by ex vivo PET/CT scans and quantified by ex vivo biodistribution studies. Results: Folate receptor-β expression was 3- to 4-fold increased in patients with fibrotic ILD, including idiopathic pulmonary fibrosis and connective tissue disease-related ILD, and significantly correlated with the degree of lung remodeling. A similar increase in the expression of folate receptor-β was observed in experimental lung fibrosis, where it also correlated with disease extent. In the mouse model of BLM-induced ILD, pulmonary accumulation of 18F-AzaFol reflected macrophage-related disease development with good correlation of folate receptor-β positivity with radiotracer uptake. In the ex vivo imaging and biodistribution studies, the maximum lung accumulation was observed at day 7 with a mean accumulation of 1.01 ± 0.30% injected activity/lung in BLM-treated vs. control animals (0.31 ± 0.06% % injected activity/lung; p < 0.01). Conclusion: Our preclinical proof-of-concept study demonstrated the potential of 18F-AzaFol as a novel imaging tool for the visualization of macrophage-driven fibrotic lung diseases., Frontiers in Immunology, 10, ISSN:1664-3224
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- 2019
- Full Text
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4. Folate Receptor-Positive Gynecological Cancer Cells: In Vitro and In Vivo Characterization.
- Author
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Siwowska, Klaudia, Schmid, Raffaella M., Cohrs, Susan, Schibli, Roger, and Müller, Cristina
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FOLIC acid ,GYNECOLOGIC cancer ,CHORIOCARCINOMA ,CANCER chemotherapy ,XENOGRAFTS ,GENE expression ,IN vitro studies ,LABORATORY mice - Abstract
The folate receptor alpha (FR) is expressed in a variety of gynecological cancer types. It has been widely used for tumor targeting with folic acid conjugates of diagnostic and therapeutic probes. The cervical KB tumor cells have evolved as the standard model for preclinical investigations of folate-based (radio) conjugates. In this study, a panel of FR-expressing human cancer cell lines-- including cervical (HeLa, KB, KB-V1), ovarian (IGROV-1, SKOV-3, SKOV-3.ip), choriocarcinoma (JAR, BeWo) and endometrial (EFE-184) tumor cells--was investigated in vitro and for their ability to grow as xenografts in mice. FR-expression levels were compared in vitro and in vivo and the cell lines were characterized by determination of the sensitivity towards commonly-used chemotherapeutics and the expression of two additional, relevant tumor markers, HER2 and L1-CAM. It was found that, besides KB cells, its multiresistant KB-V1 subclone as well as the ovarian cancer cell lines, IGROV-1 and SKOV-3.ip, could be used as potentially more relevant preclinical models. They would allow addressing specific questions such as the therapeutic efficacy of FR-targeting agents in tumor (mouse) models of multi-resistance and in mouse models of metastases formation. [ABSTRACT FROM AUTHOR]
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- 2017
- Full Text
- View/download PDF
5. Promising potential of [Lu-177]Lu-DOTA-folate to enhance tumor response to immunotherapy-a preclinical study using a syngeneic breast cancer model
- Author
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Guzik, Patrycja, Siwowska, Klaudia, Fang, Hsin-Yu, Cohrs, Susan, Bernhardt, Peter, Schibli, Roger, and Müller, Cristina
- Subjects
Folate receptor ,[Lu-177]Lu-DOTA-folate ,CTLA-4 ,Immunotherapy ,3. Good health ,NF9006 breast tumor cells - Abstract
Purpose It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [Lu-177]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy. Methods In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [Lu-177]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [Lu-177]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 x 200 mu g; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment. Results [Lu-177]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [Lu-177]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [Lu-177]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls. Conclusion Application of [Lu-177]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates., European Journal of Nuclear Medicine and Molecular Imaging, 48 (4), ISSN:1619-7070, ISSN:1619-7089
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