Feasibility of Ga-68-labeled Siglec-9 peptide for the imaging of acute lung inflammation: a pilot study in a porcine model of acute respiratory distress syndrome

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art_RETAMAL_Feasibility_of_Ga68labeled_Siglec9_peptide_for_the_imaging_2016.PDF (914.69 KB)
Citações na Scopus
Tipo de produção
article
Data de publicação
2016
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
E-CENTURY PUBLISHING CORP
Autores
RETAMAL, Jaime
SORENSEN, Jens
LUBBERINK, Mark
SUAREZ-SIPMANN, Fernando
FEINSTEIN, Ricardo
JALKANEN, Sirpa
ANTONI, Gunnar
HEDENSTIERNA, Goran
ROIVAINEN, Anne
Citação
AMERICAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, v.6, n.1, p.18-31, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 [O-15]water PET-CT (10 min) was followed by dynamic (90 min) and whole-body examination using VAP-1 targeting Ga-68-labeled 1,4,7,10-tetraaza cyclododecane-1,4,7-tris-acetic acid-10-ethylene glycol-conjugated Siglec-9 motif peptide ([Ga-68]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. [Ga-68]Ga-DOTA-Siglec-9 PET showed significant uptake in lungs, kidneys and urinary bladder. Normalization of the net uptake rate (K-i) for the tissue perfusion resulted in 4-fold higher uptake rate of [Ga-68]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 [Ga-68]Ga-DOTA-Siglec-9 PET when using kinetic modeling and normalization for tissue perfusion.
Palavras-chave
Ga-68, PET, lung inflammation, Siglec-9, VAP-1
URI
https://observatorio.fm.usp.br/handle/OPI/20359
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Coleções
Artigos e Materiais de Revistas Científicas - LIM/09