title: Assessment of blood flow with (68)Ga-DOTA PET in experimental inflammation: a validation study using (15)O-water.
abstract: Increased blood flow and vascular permeability are key events in inflammation. Based on the fact that Gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (Gd-DOTA) is commonly used in magnetic resonance (MR) imaging of blood flow (perfusion), we evaluated the feasibility of its Gallium-68 labeled DOTA analog ((68)Ga-DOTA) for positron emission tomography (PET) imaging of blood flow in experimental inflammation. Adult, male Sprague-Dawley rats with turpentine oil induced sterile skin/muscle inflammation were anesthetized with isoflurane, and imaged under rest and adenosine-induced hyperemia by means of dynamic 2-min Oxygen-15 labeled water (H2 (15)O) and 30-min (68)Ga-DOTA PET. For the quantification of PET data, regions of interest (ROIs) were defined in the focus of inflammation, healthy muscle, myocardium and heart left ventricle. Radioactivity concentration in the ROIs versus time after injection was determined for both tracers and blood flow was calculated using image-derived input. According to the H2 (15)O PET, blood flow was 0.69 ± 0.15 ml/min/g for inflammation and 0.15 ± 0.03 ml/min/g for muscle during rest. The blood flow remained unchanged during adenosine-induced hyperemia 0.67 ± 0.11 and 0.12 ± 0.03 ml/min/g for inflammation and muscle, respectively, indicating that adenosine has little effect on blood flow in peripheral tissues in rats. High focal uptake of (68)Ga-DOTA was seen at the site of inflammation throughout the 30-min PET imaging. According to the (68)Ga-DOTA PET, blood flow measured as the blood-to-tissue transport rate (K1) was 0.60 ± 0.07 ml/min/g for inflammation and 0.14 ± 0.06 ml/min/g for muscle during rest and 0.63 ± 0.08 ml/min/g for inflammation and 0.09 ± 0.04 ml/min/g for muscle during adenosine-induced hyperemia. The H2 (15)O-based blood flow and (68)Ga-DOTA-based K1 values correlated well (r = 0.94, P < 0.0001). These results show that (68)Ga-DOTA PET imaging is useful for the quantification of increased blood flow induced by inflammation.
authors.affiliation: Turku PET Centre Turku, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Autio
authors.affiliation: Turku PET Centre Turku, Finland ; Heart Center, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.affiliation: Turku PET Centre Turku, Finland ; Department of Medical Physics, Faculty of Medicine, Kagawa University Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kudomi
authors.affiliation: Turku PET Centre Turku, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Saanijoki
authors.affiliation: Turku PET Centre Turku, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Johansson
authors.affiliation: Turku PET Centre Turku, Finland ; Turku Center for Disease Modeling, University of Turku Turku, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Liljenbäck
authors.affiliation: Turku PET Centre Turku, Finland.
authors.forename: Miikka
authors.initials: M
authors.lastname: Tarkia
authors.affiliation: Turku PET Centre Turku, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Oikonen
authors.affiliation: Turku PET Centre Turku, Finland.
authors.forename: Hannu T
authors.initials: HT
authors.lastname: Sipilä
authors.affiliation: Turku PET Centre Turku, Finland ; Turku Center for Disease Modeling, University of Turku Turku, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
keywords: Blood flow; DOTA; Gallium-68; Oxygen-15 water; PET; inflammation; rat