Detection of leukotriene receptor CysLT1R in inflammatory diseases by molecular imaging with near-infrared fluorescence-based contrast agents.
Mol Imaging
; 10(2): 81-90, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21439253
ABSTRACT
As leukotriene D4 receptor CysLT1R upregulation is an early event in inflammatory processes, specific detection of CysLT1R via molecular imaging might be a promising diagnostic tool for inflammatory diseases. We coupled a specific anti-CysLT1R IgG antibody to near-infrared (NIR) hemicyanine fluorophore DY-734. The fluorophore was also coupled to unspecific rabbit-IgG antibody or corresponding Fab fragments. Expression of CysLT1R in HL-60 human promyelocytic leukemia cells in vitro could be proven by reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, and flow cytometry. Detection of the probes by flow cytometry showed that CysLT1R*DY-734 probe binds distinctly stronger to HL-60 cells than IgG*DY-734. Induction of ear edema in mice was conducted to test signaling of the synthesized probes in vivo. A markedly higher fluorescence intensity was observed in the edematous region than in the healthy region by a whole-body imaging system. Semiquantitative analysis showed that CysLT1R*DY-734 and Fab-CysLT1R*DY-734 probes bind 1.9- and 1.2-fold stronger, respectively, than the unspecific probes. Biodistribution studies revealed an enrichment of full-length IgG probes in liver and spleen, whereas Fab-containing probes are mostly found in liver and kidneys. Taken together, we present an approach that might improve early diagnosis of inflammatory diseases in the long term.
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Base de dados:
MEDLINE
Assunto principal:
Receptores de Leucotrienos
/
Meios de Contraste
/
Edema
/
Imagem Molecular
/
Inflamação
/
Raios Infravermelhos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Mol Imaging
Assunto da revista:
DIAGNOSTICO POR IMAGEM
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha