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Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis

PURPOSE: Endometriosis is a chronic condition characterized by high fibrotic content and affecting about 10% of women during their reproductive years. Yet, no clinically approved agents are available for non-invasive endometriosis detection. The purpose of this study was to investigate the utility o...

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Autores principales: Talebloo, Nazanin, Bernal, Maria Ariadna Ochoa, Kenyon, Elizabeth, Mallett, Christiane L., Fazleabas, Asgerally, Moore, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598151/
https://www.ncbi.nlm.nih.gov/pubmed/37418136
http://dx.doi.org/10.1007/s11307-023-01833-6
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author Talebloo, Nazanin
Bernal, Maria Ariadna Ochoa
Kenyon, Elizabeth
Mallett, Christiane L.
Fazleabas, Asgerally
Moore, Anna
author_facet Talebloo, Nazanin
Bernal, Maria Ariadna Ochoa
Kenyon, Elizabeth
Mallett, Christiane L.
Fazleabas, Asgerally
Moore, Anna
author_sort Talebloo, Nazanin
collection PubMed
description PURPOSE: Endometriosis is a chronic condition characterized by high fibrotic content and affecting about 10% of women during their reproductive years. Yet, no clinically approved agents are available for non-invasive endometriosis detection. The purpose of this study was to investigate the utility of a gadolinium-based collagen type I targeting probe (EP-3533) to non-invasively detect endometriotic lesions using magnetic resonance imaging (MRI). Previously, this probe has been used for detection and staging of fibrotic lesions in the liver, lung, heart, and cancer. In this study we evaluate the potential of EP-3533 for detecting endometriosis in two murine models and compare it with a non-binding isomer (EP-3612). PROCEDURES: For imaging, we utilized two GFP-expressing murine models of endometriosis (suture model and injection model) injected intravenously with EP3533 or EP-33612. Mice were imaged before and after bolus injection of the probes. The dynamic signal enhancement of MR T1 FLASH images was analyzed, normalized, and quantified, and the relative location of lesions was validated through ex vivo fluorescence imaging. Subsequently, the harvested lesions were stained for collagen, and their gadolinium content was quantified by inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: We showed that EP-3533 probe increased the signal intensity in T1-weighted images of endometriotic lesions in both models of endometriosis. Such enhancement was not detected in the muscles of the same groups or in endometriotic lesions of mice injected with EP-3612 probe. Consequentially, control tissues had significantly lower gadolinium content, compared to the lesions in experimental groups. Probe accumulation was similar in endometriotic lesions of either model. CONCLUSIONS: This study provides evidence for feasibility of targeting collagen type I in the endometriotic lesions using EP3533 probe. Our future work includes investigation of the utility of this probe for therapeutic delivery in endometriosis to inhibit signaling pathways that cause the disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11307-023-01833-6.
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spelling pubmed-105981512023-10-26 Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis Talebloo, Nazanin Bernal, Maria Ariadna Ochoa Kenyon, Elizabeth Mallett, Christiane L. Fazleabas, Asgerally Moore, Anna Mol Imaging Biol Research Article PURPOSE: Endometriosis is a chronic condition characterized by high fibrotic content and affecting about 10% of women during their reproductive years. Yet, no clinically approved agents are available for non-invasive endometriosis detection. The purpose of this study was to investigate the utility of a gadolinium-based collagen type I targeting probe (EP-3533) to non-invasively detect endometriotic lesions using magnetic resonance imaging (MRI). Previously, this probe has been used for detection and staging of fibrotic lesions in the liver, lung, heart, and cancer. In this study we evaluate the potential of EP-3533 for detecting endometriosis in two murine models and compare it with a non-binding isomer (EP-3612). PROCEDURES: For imaging, we utilized two GFP-expressing murine models of endometriosis (suture model and injection model) injected intravenously with EP3533 or EP-33612. Mice were imaged before and after bolus injection of the probes. The dynamic signal enhancement of MR T1 FLASH images was analyzed, normalized, and quantified, and the relative location of lesions was validated through ex vivo fluorescence imaging. Subsequently, the harvested lesions were stained for collagen, and their gadolinium content was quantified by inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: We showed that EP-3533 probe increased the signal intensity in T1-weighted images of endometriotic lesions in both models of endometriosis. Such enhancement was not detected in the muscles of the same groups or in endometriotic lesions of mice injected with EP-3612 probe. Consequentially, control tissues had significantly lower gadolinium content, compared to the lesions in experimental groups. Probe accumulation was similar in endometriotic lesions of either model. CONCLUSIONS: This study provides evidence for feasibility of targeting collagen type I in the endometriotic lesions using EP3533 probe. Our future work includes investigation of the utility of this probe for therapeutic delivery in endometriosis to inhibit signaling pathways that cause the disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11307-023-01833-6. Springer International Publishing 2023-07-07 2023 /pmc/articles/PMC10598151/ /pubmed/37418136 http://dx.doi.org/10.1007/s11307-023-01833-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Talebloo, Nazanin
Bernal, Maria Ariadna Ochoa
Kenyon, Elizabeth
Mallett, Christiane L.
Fazleabas, Asgerally
Moore, Anna
Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis
title Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis
title_full Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis
title_fullStr Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis
title_full_unstemmed Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis
title_short Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis
title_sort detection of endometriosis lesions using gd-based collagen i targeting probe in murine models of endometriosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10598151/
https://www.ncbi.nlm.nih.gov/pubmed/37418136
http://dx.doi.org/10.1007/s11307-023-01833-6
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