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[18F]fluciclatide- Autoradiography study of angiogenesis in abdominal aortic aneurysm
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kärlkirurgi.
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2013 (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Ort, förlag, år, upplaga, sidor
2013.
Nyckelord [en]
AAA, PET, 18F-Fluciclatide, integrin alfaVbeta3, angiogenesis, pathophysiology
Nationell ämneskategori
Kirurgi Fysiologi Annan medicinsk bioteknologi
Identifikatorer
URN: urn:nbn:se:uu:diva-197432OAI: oai:DiVA.org:uu-197432DiVA, id: diva2:612844
Tillgänglig från: 2013-03-25 Skapad: 2013-03-25 Senast uppdaterad: 2018-01-11
Ingår i avhandling
1. Abdominal Aortic Aneurysm: Molecular Imaging Studies of Pathophysiology
Öppna denna publikation i ny flik eller fönster >>Abdominal Aortic Aneurysm: Molecular Imaging Studies of Pathophysiology
2013 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2013. s. 111
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 899
Nyckelord
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
Nationell ämneskategori
Medicin och hälsovetenskap Kirurgi Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Forskningsämne
Kirurgi; Medicinsk radiofysik
Identifikatorer
urn:nbn:se:uu:diva-194663 (URN)978-91-554-8656-3 (ISBN)
Disputation
2013-05-31, Auditorium Minus, Museum Gustavianum, Akademigatan 3, Uppsala, 13:15 (Svenska)
Opponent
Handledare
Tillgänglig från: 2013-05-08 Skapad: 2013-02-18 Senast uppdaterad: 2013-08-30Bibliografiskt granskad

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Tegler, GustafWallgren, AnnaCarinEstrada, SergioWanhainen, AndersBjörck, MartinSörensen, JensAntoni, Gunnar
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KärlkirurgiMolekylär och morfologisk patologiPlattformen för preklinisk PETEnheten för nuklearmedicin och PETInstitutionen för läkemedelskemi
KirurgiFysiologiAnnan medicinsk bioteknologi

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