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4D-PET/CT with [11C]-PK11195 and [11C]-D-deprenyl does not identify the chronic inflammation in asymptomatic abdominal aortic aneurysms
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 Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. (Department of Pathology)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
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2013 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 45, no 4, 351-356 p.Article in journal (Refereed) Published
Abstract [en]

Objectives

The aim of this study was to investigate the relevance of inflammation in the pathogenesis of abdominal aortic aneurysm (AAA) in vivo with two novel positron emission tomography (PET) tracers: [11C]-PK11195 which targets the translocator protein (18 kDa) expressed on macrophages and [11C]-d-deprenyl with a yet unknown target receptor expressed in chronic inflammation.

Design

Prospective clinical study.

Materials/methods

Five patients were examined with [11C]-PK11195-positron emission tomography/computed tomography (PET/CT) and 10 with [11C]-d-deprenyl-PET/CT. Nine large AAAs (54–66 mm) scheduled for repair and six small AAA (35–44 mm). All 15 patients were male and the AAAs were all asymptomatic. Regional activity was measured as standardised uptake values (SUVs) and retention index was calculated. Biopsies were taken from the aneurysm wall for histological examinations, in the nine patients operated on.

Results

No aortic uptake was recorded on the visual inspection, neither with [11C]-PK11195 nor with [11C]-d-deprenyl. For [11C]-PK11195 the median SUV of the AAA wall was 0.9 (range 0.8–1.0) and for [11C]-d-deprenyl, 0.7 (range 0.4–1.2). No increased uptake was seen in the aneurysmal infrarenal aorta compared with the non-aneurysmal suprarenal aorta. Histological examination of the aneurysm wall showed high inflammatory cell infiltration with lymphocytes and macrophages.

Conclusions

The chronic inflammation observed in the vessel wall was not detectable with [11C]-PK11195 and [11C]-d-deprenyl. In order to study the relevance of the inflammation in the pathogenesis of AAA in vivo other PET tracers need to be investigated.

Place, publisher, year, edition, pages
2013. Vol. 45, no 4, 351-356 p.
Keyword [en]
AAA, PET, 11C-PK1195, 11C-D-deprenyl, pathophysiology
National Category
Surgery Physiology Other Medical Biotechnology
Research subject
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-197429DOI: 10.1016/j.ejvs.2013.01.011ISI: 000316924900007PubMedID: 23394769OAI: oai:DiVA.org:uu-197429DiVA: diva2:612836
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2017-12-06Bibliographically approved
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)
Opponent
Supervisors
Available from: 2013-05-08 Created: 2013-02-18 Last updated: 2013-08-30Bibliographically approved

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Tegler, GustafSörensen, JensBjörck, MartinWanhainen, Anders

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