Molecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxide
<p>One approach that has demonstrated success in the field of molecular imaging utilizes microparticles of iron oxide (MPIO) conjugated to specific antibodies and/or peptides to provide contrast effects on MRI in relation to the molecular expression of a specified target. The experimental aims...
| Những tác giả chính: | , |
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| Tác giả khác: | |
| Định dạng: | Luận văn |
| Ngôn ngữ: | English |
| Được phát hành: |
2010
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| Những chủ đề: |
| _version_ | 1826315686583992320 |
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| author | Akhtar, A Asim Akhtar |
| author2 | Choudhury, R |
| author_facet | Choudhury, R Akhtar, A Asim Akhtar |
| author_sort | Akhtar, A |
| collection | OXFORD |
| description | <p>One approach that has demonstrated success in the field of molecular imaging utilizes microparticles of iron oxide (MPIO) conjugated to specific antibodies and/or peptides to provide contrast effects on MRI in relation to the molecular expression of a specified target. The experimental aims of this thesis were 1) to investigate the ability of VCAM-1 and P-selectin targeted MPIO to detect the expression of VCAM-1 and P-selectin on the activated endothelium in-vitro and in-vivo in mouse models of renal and cerebral ischemia reperfusion injury, and 2) develop a novel contrast agent for imaging αvβ3-integrin expression in angiogenesis using RGD peptide conjugated MPIO (RGD-MPIO) in-vitro.</p><p>MPIO (1.0 µm) were conjugated to monoclonal antibodies against VCAM-1 (VCAM-MPIO) or P-selectin (PSEL-MPIO). In vitro, MPIO bound in a dose-dependent manner to tumor necrosis factor (TNF)-alpha stimulated sEND-1 endothelial cells when conjugated to VCAM-1 (R² = 0.88, P<0.01) and P-selectin antibodies (R² = 0.93, P<0.01), reflecting molecular VCAM-1 and P-selectin mRNA and protein expression. Mice subjected to unilateral, transient (30 minutes) renal ischemia and subsequent reperfusion received intravenous VCAM-MPIO and PSEL-MPIO (4.5 mg iron/kg body weight). In ischemic kidneys, MR related contrast effects of VCAM-MPIO were 4-fold higher than unclamped kidneys (P<0.01) and 1.5-fold higher than clamped kidneys of PSEL-MPIO injected mice (P<0.05). VCAM-MPIO binding was less evident in IRI kidneys pre-treated with VCAM-1 antibody (P<0.001). VCAM-1 mRNA expression and VCAM-MPIO contrast volume were highly correlated (R² = 0.901, P<0.01), indicating that quantification of contrast volume reflected renal VCAM-1 transcription. In mice subjected to cerebral ischemia, contrast volume was 11-fold greater in animals injected with VCAM-MPIO versus control IgG-MPIO (P<0.05). Finally, S-nitroso-N-acetylpenicillamine (SNAP) stimulated HUVEC-C cells, which express αvβ3-integrin, showed 44-fold greater RGD-MPIO binding than unstimulated cells (P<0.001) and 4-fold greater RGD-MPIO binding than SNAP stimulated cells blocked with soluble RGD peptide (P<0.001) in-vitro.</p><p>This thesis demonstrated that targeted MPIO exhibited contrast effects that defined and quantified the molecular expression of specific targets through the use of high-resolution MRI in in-vitro and in-vivo models of vascular inflammation.</p> |
| first_indexed | 2024-03-06T18:58:37Z |
| format | Thesis |
| id | oxford-uuid:12bf8e4f-2909-4715-a6fe-bf42d9d8355a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:30:37Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:12bf8e4f-2909-4715-a6fe-bf42d9d8355a2024-12-01T13:58:45ZMolecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxideThesishttp://purl.org/coar/resource_type/c_db06uuid:12bf8e4f-2909-4715-a6fe-bf42d9d8355aStrokeRadiologyMedical SciencesAdvanced materialsVascular researchCardiovascular diseaseDisease preventionEnglishOxford University Research Archive - Valet2010Akhtar, AAsim AkhtarChoudhury, R<p>One approach that has demonstrated success in the field of molecular imaging utilizes microparticles of iron oxide (MPIO) conjugated to specific antibodies and/or peptides to provide contrast effects on MRI in relation to the molecular expression of a specified target. The experimental aims of this thesis were 1) to investigate the ability of VCAM-1 and P-selectin targeted MPIO to detect the expression of VCAM-1 and P-selectin on the activated endothelium in-vitro and in-vivo in mouse models of renal and cerebral ischemia reperfusion injury, and 2) develop a novel contrast agent for imaging αvβ3-integrin expression in angiogenesis using RGD peptide conjugated MPIO (RGD-MPIO) in-vitro.</p><p>MPIO (1.0 µm) were conjugated to monoclonal antibodies against VCAM-1 (VCAM-MPIO) or P-selectin (PSEL-MPIO). In vitro, MPIO bound in a dose-dependent manner to tumor necrosis factor (TNF)-alpha stimulated sEND-1 endothelial cells when conjugated to VCAM-1 (R² = 0.88, P<0.01) and P-selectin antibodies (R² = 0.93, P<0.01), reflecting molecular VCAM-1 and P-selectin mRNA and protein expression. Mice subjected to unilateral, transient (30 minutes) renal ischemia and subsequent reperfusion received intravenous VCAM-MPIO and PSEL-MPIO (4.5 mg iron/kg body weight). In ischemic kidneys, MR related contrast effects of VCAM-MPIO were 4-fold higher than unclamped kidneys (P<0.01) and 1.5-fold higher than clamped kidneys of PSEL-MPIO injected mice (P<0.05). VCAM-MPIO binding was less evident in IRI kidneys pre-treated with VCAM-1 antibody (P<0.001). VCAM-1 mRNA expression and VCAM-MPIO contrast volume were highly correlated (R² = 0.901, P<0.01), indicating that quantification of contrast volume reflected renal VCAM-1 transcription. In mice subjected to cerebral ischemia, contrast volume was 11-fold greater in animals injected with VCAM-MPIO versus control IgG-MPIO (P<0.05). Finally, S-nitroso-N-acetylpenicillamine (SNAP) stimulated HUVEC-C cells, which express αvβ3-integrin, showed 44-fold greater RGD-MPIO binding than unstimulated cells (P<0.001) and 4-fold greater RGD-MPIO binding than SNAP stimulated cells blocked with soluble RGD peptide (P<0.001) in-vitro.</p><p>This thesis demonstrated that targeted MPIO exhibited contrast effects that defined and quantified the molecular expression of specific targets through the use of high-resolution MRI in in-vitro and in-vivo models of vascular inflammation.</p> |
| spellingShingle | Stroke Radiology Medical Sciences Advanced materials Vascular research Cardiovascular disease Disease prevention Akhtar, A Asim Akhtar Molecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxide |
| title | Molecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxide |
| title_full | Molecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxide |
| title_fullStr | Molecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxide |
| title_full_unstemmed | Molecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxide |
| title_short | Molecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxide |
| title_sort | molecular magnetic resonance imaging of vascular inflammation using microparticles of iron oxide |
| topic | Stroke Radiology Medical Sciences Advanced materials Vascular research Cardiovascular disease Disease prevention |
| work_keys_str_mv | AT akhtara molecularmagneticresonanceimagingofvascularinflammationusingmicroparticlesofironoxide AT asimakhtar molecularmagneticresonanceimagingofvascularinflammationusingmicroparticlesofironoxide |