Detection of Leukotriene Receptor CysLTR in Inflammatory Diseases by Molecular Imaging with Near-Infrared Fluorescence-Based Contrast Agents

As leukotriene D 4 receptor CysLT 1 R upregulation is an early event in inflammatory processes, specific detection of CysLT 1 R via molecular imaging might be a promising diagnostic tool for inflammatory diseases. We coupled a specific anti-CysLT 1 R IgG antibody to near-infrared (NIR) hemicyanine f...

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Bibliographic Details
Main Authors: Corinna Busch, Marta Passon, Matthias Wenzel, Ines Socher, Werner A. Kaiser, Ingrid Hilger
Format: Article
Language:English
Published: Hindawi - SAGE Publishing 2011-03-01
Series:Molecular Imaging
Online Access:https://doi.org/10.2310/7290.2010.00023
Description
Summary:As leukotriene D 4 receptor CysLT 1 R upregulation is an early event in inflammatory processes, specific detection of CysLT 1 R via molecular imaging might be a promising diagnostic tool for inflammatory diseases. We coupled a specific anti-CysLT 1 R 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 CysLT 1 R 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 CysLT 1 R * 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 CysLT 1 R * DY-734 and Fab-CysLT 1 R * 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.
ISSN:1536-0121