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[18F]fluciclatide- Autoradiography study of angiogenesis in abdominal aortic aneurysm
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
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2013 (English)Manuscript (preprint) (Other academic)
Place, publisher, year, edition, pages
2013.
Keyword [en]
AAA, PET, 18F-Fluciclatide, integrin alfaVbeta3, angiogenesis, pathophysiology
National Category
Surgery Physiology Other Medical Biotechnology
Identifiers
URN: urn:nbn:se:uu:diva-197432OAI: oai:DiVA.org:uu-197432DiVA: diva2:612844
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2015-09-24
In thesis
1. Abdominal Aortic Aneurysm: Molecular Imaging Studies of Pathophysiology
Open this publication in new window or tab >>Abdominal Aortic Aneurysm: Molecular Imaging Studies of Pathophysiology
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The pathological process behind abdominal aortic aneurysm (AAA) formation is poorly understood and difficult to study. The aim of the thesis was to study the pathophysiology of AAA formation with positron emission tomography (PET) technology, a molecular imaging technique, allowing in vivo studies of pathophysiological changes.

In study I 18F-FDG, a glucose analogue, was tested. It had previously been reported as a useful tracer studying inflammation in AAAs. These studies included, however, foremost large, symptomatic, and inflammatory AAAs. In the present study on five small and seven large asymptomatic AAAs, no increase in 18F-FDG uptake could be revealed in vivo.

In study II 11C-PK11195, a macrophage tracer, and 11C-D-deprenyl, an unspecific inflammatory tracer, previously never tested on asymptomatic AAAs, were tested in vivo on five and 10 AAA-patients respectively, without signs of increased levels of inflammatory activity in the aorta.

In study III several tracers were screened in vitro through autoradiography on AAA tissue. [18F]fluciclatide, targeting the integrin αVβ3 receptor upregulated in angiogenesis, was the only tracer with an increased uptake.

In study IV [18F]fluciclatide-autoradiography was performed on AAA tissue from five patients and non-aneurysmal aortic tissue obtained from five age and sex matched organ donors. The study showed a 56% increased specific uptake in AAA, although not significant (P=0.136). Immunohistochemical revealed inflammatory cell foci in close relation to the vessels.

In conclusion, PET has potential to elucidate the pathophysiology of AAA formation. For the large group of small asymptomatic AAAs, 18F-FDG is not suitable, as the chronic inflammation in asymptomatic AAA is not sufficiently metabolically active. Furthermore, 11C-PK11195 and 11C-D-deprenyl were unable to show the chronic inflammation seen in asymptomatic AAA.

The interesting finding with uptake of [18F]fluciclatide showed that angiogenesis may be imaged in large asymptomatic AAAs in vitro, through the integrin αVβ3 receptor. Thus, it is likely that future studies of the role of angiogenesis in AAA formation in vivo, in small AAAs, could use this target site. The development of an integrin αVβ3 receptor tracer, preferably with higher affinity, is in progress for further in vitro and in vivo studies.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 111 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 899
Keyword
Abdominal aortic aneurysm, AAA, Positron emission tomography, PET, Molecular Imaging, Pathophysiology, Autoradiography, Angiogenesis, integrin alphaVbeta3, FDG, 18F-FDG, 11C-PK11195, 11C-D-deprenyl, [18F]fluciclatide, Fluciclatide, Bukaortaaneurysm, Molekylär bilddiagnostik, Patofysiologi, PET, Autoradiografi, Angiogenes
National Category
Medical and Health Sciences Surgery Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Surgery; Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-194663 (URN)978-91-554-8656-3 (ISBN)
Public defence
2013-05-31, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 13:15 (Swedish)
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Supervisors
Available from: 2013-05-08 Created: 2013-02-18 Last updated: 2013-08-30Bibliographically approved

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Tegler, GustafWallgren, AnnaCarinEstrada, SergioWanhainen, AndersBjörck, MartinSörensen, JensAntoni, Gunnar

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Vascular SurgeryMolecular and Morphological PathologyPreclinical PET PlatformSection of Nuclear Medicine and PETDepartment of Medicinal Chemistry
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