title: Feasibility of (68)Ga-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome.
abstract: There is an unmet need for noninvasive, specific and quantitative imaging of inherent inflammatory activity. Vascular adhesion protein-1 (VAP-1) translocates to the luminal surface of endothelial cells upon inflammatory challenge. We hypothesized that in a porcine model of acute respiratory distress syndrome (ARDS), positron emission tomography (PET) with sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) based imaging agent targeting VAP-1 would allow quantification of regional pulmonary inflammation. ARDS was induced by lung lavages and injurious mechanical ventilation. Hemodynamics, respiratory system compliance (Crs) and blood gases were monitored. Dynamic examination using [(15)O]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting (68)Ga-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([(68)Ga]Ga-DOTA-Siglec-9). The animals received an anti-VAP-1 antibody for post-mortem immunohistochemistry assay of VAP-1 receptors. Tissue samples were collected post-mortem for the radioactivity uptake, histology and immunohistochemistry assessment. Marked reduction of oxygenation and Crs, and higher degree of inflammation were observed in ARDS animals. [(68)Ga]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (Ki) for the tissue perfusion resulted in 4-fold higher uptake rate of [(68)Ga]Ga-DOTA-Siglec-9 in the ARDS lungs. Immunohistochemistry showed positive VAP-1 signal in the injured lungs. Detection of pulmonary inflammation associated with a porcine model of ARDS was possible with [(68)Ga]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion.
authors.affiliation: Department of Surgical Sciences, Hedenstierna laboratory, Uppsala UniversityUppsala, Sweden; Departament de Medicina Intensiva, Pontificia Universidad Católica de ChileSantiago, Chile.
authors.forename: Jaime
authors.initials: J
authors.lastname: Retamal
authors.affiliation: Department of Surgical Sciences, Section of Nuclear Medicine and PET, Uppsala University Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
authors.affiliation: Department of Surgical Sciences, Section of Nuclear Medicine and PET, Uppsala University Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.affiliation: Department of Surgical Sciences, Hedenstierna laboratory, Uppsala UniversityUppsala, Sweden; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos IIIMadrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Suarez-Sipmann
authors.affiliation: Department of Surgical Sciences, Hedenstierna laboratory, Uppsala UniversityUppsala, Sweden; Pulmonary Divison, Heart Institute (Incor) Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloBrazil.
authors.forename: João Batista
authors.initials: JB
authors.lastname: Borges
authors.affiliation: The Swedish National Veterinary Institute Sweden.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Feinstein
authors.affiliation: MediCity Research Laboratory, Department of Medical Microbiology and Immunology, University of Turku Turku, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Jalkanen
authors.affiliation: Department of Medicinal Chemistry, Uppsala University Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
authors.affiliation: Department of Surgical Sciences, Hedenstierna laboratory, Uppsala University Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Hedenstierna
authors.affiliation: Turku PET Centre, University of Turku and Turku University HospitalTurku, Finland; Turku Center for Disease Modelling, University of TurkuFurku, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Roivainen
authors.affiliation: Department of Surgical Sciences, Hedenstierna laboratory, Uppsala University Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Larsson
authors.affiliation: Department of Surgical Sciences, Section of Nuclear Medicine and PET, Uppsala University Uppsala, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Velikyan
keywords: 68Ga; PET; Siglec-9; VAP-1; lung inflammation