Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel F-Folate Radiotracer
Folate receptor β (FR-β) is overexpressed on activated, but not resting, macrophages involved in a variety of inflammatory and autoimmune diseases. A pivotal step in atherogenesis is the subendothelial accumulation of macrophages. In nascent lesions, they coordinate the scavenging of lipids and cell...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2014-03-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2013.00074 |
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| author | Adrienne Müller Katharina Beck Zoran Rancic Cristina Müller Cindy R. Fischer Thomas Betzel Philipp A. Kaufmann Roger Schibli Stefanie D. Kramer Simon M. Ametamey |
| author_facet | Adrienne Müller Katharina Beck Zoran Rancic Cristina Müller Cindy R. Fischer Thomas Betzel Philipp A. Kaufmann Roger Schibli Stefanie D. Kramer Simon M. Ametamey |
| author_sort | Adrienne Müller |
| collection | DOAJ |
| description | Folate receptor β (FR-β) is overexpressed on activated, but not resting, macrophages involved in a variety of inflammatory and autoimmune diseases. A pivotal step in atherogenesis is the subendothelial accumulation of macrophages. In nascent lesions, they coordinate the scavenging of lipids and cellular debris to define the likelihood of plaque inflammation and eventually rupture. In this study, we determined the presence of FR-β-expressing macrophages in atherosclerotic lesions by the use of a fluorine-18-labeled folate-based radiotracer. Human endarterectomized specimens were used to measure gene expression levels of FR-β and CD68. Increased FR-β and CD68 levels were found in atherosclerotic plaques compared to normal artery walls by quantitative real-time polymerase chain reaction. Western blotting and immunohistochemistry demonstrated prominent FR-β protein levels in plaques. FR- β-positive cells colocalized with activated macrophages (CD68) in plaque tissue. Carotid sections incubated with 3′-aza-2′- [ 18 F]fluorofolic acid displayed increased accumulation in atherosclerotic plaques through in vitro autoradiography. Specific binding of the radiotracer correlated with FR-β-expressing macrophages. These results demonstrate high FR-β expression in atherosclerotic lesions of human carotid tissue correlating with CD68-positive macrophages. Areas of high 3′-aza-2′-[ 18 F]fluorofolic acid binding within the lesions represented FR-β-expressing macrophages. Selectively targeting FR-β-positive macrophages through folate-based radiopharmaceuticals may be useful for noninvasive imaging of plaque inflammation. |
| format | Article |
| id | doaj-art-13c6c2694b534b779505b9ad78f298fc |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2014-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-13c6c2694b534b779505b9ad78f298fc2025-01-03T00:12:13ZengSAGE PublishingMolecular Imaging1536-01212014-03-011310.2310/7290.2013.0007410.2310_7290.2013.00074Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel F-Folate RadiotracerAdrienne MüllerKatharina BeckZoran RancicCristina MüllerCindy R. FischerThomas BetzelPhilipp A. KaufmannRoger SchibliStefanie D. KramerSimon M. AmetameyFolate receptor β (FR-β) is overexpressed on activated, but not resting, macrophages involved in a variety of inflammatory and autoimmune diseases. A pivotal step in atherogenesis is the subendothelial accumulation of macrophages. In nascent lesions, they coordinate the scavenging of lipids and cellular debris to define the likelihood of plaque inflammation and eventually rupture. In this study, we determined the presence of FR-β-expressing macrophages in atherosclerotic lesions by the use of a fluorine-18-labeled folate-based radiotracer. Human endarterectomized specimens were used to measure gene expression levels of FR-β and CD68. Increased FR-β and CD68 levels were found in atherosclerotic plaques compared to normal artery walls by quantitative real-time polymerase chain reaction. Western blotting and immunohistochemistry demonstrated prominent FR-β protein levels in plaques. FR- β-positive cells colocalized with activated macrophages (CD68) in plaque tissue. Carotid sections incubated with 3′-aza-2′- [ 18 F]fluorofolic acid displayed increased accumulation in atherosclerotic plaques through in vitro autoradiography. Specific binding of the radiotracer correlated with FR-β-expressing macrophages. These results demonstrate high FR-β expression in atherosclerotic lesions of human carotid tissue correlating with CD68-positive macrophages. Areas of high 3′-aza-2′-[ 18 F]fluorofolic acid binding within the lesions represented FR-β-expressing macrophages. Selectively targeting FR-β-positive macrophages through folate-based radiopharmaceuticals may be useful for noninvasive imaging of plaque inflammation.https://doi.org/10.2310/7290.2013.00074 |
| spellingShingle | Adrienne Müller Katharina Beck Zoran Rancic Cristina Müller Cindy R. Fischer Thomas Betzel Philipp A. Kaufmann Roger Schibli Stefanie D. Kramer Simon M. Ametamey Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel F-Folate Radiotracer Molecular Imaging |
| title | Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel F-Folate Radiotracer |
| title_full | Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel F-Folate Radiotracer |
| title_fullStr | Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel F-Folate Radiotracer |
| title_full_unstemmed | Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel F-Folate Radiotracer |
| title_short | Imaging Atherosclerotic Plaque Inflammation via Folate Receptor Targeting Using a Novel F-Folate Radiotracer |
| title_sort | imaging atherosclerotic plaque inflammation via folate receptor targeting using a novel f folate radiotracer |
| url | https://doi.org/10.2310/7290.2013.00074 |
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