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Detection of leukotriene receptor CysLT1R in inflammatory diseases by molecular imaging with near-infrared fluorescence-based contrast agents.
- Source :
-
Molecular imaging [Mol Imaging] 2011 Apr; Vol. 10 (2), pp. 81-90. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
Edema pathology
Fluorescence
Fluorescent Dyes chemistry
Fluorescent Dyes metabolism
HL-60 Cells
Humans
Immunoglobulin G immunology
Inflammation pathology
Male
Mice
Rabbits
Tissue Distribution
Contrast Media
Edema metabolism
Inflammation metabolism
Infrared Rays
Molecular Imaging methods
Receptors, Leukotriene metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1536-0121
- Volume :
- 10
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular imaging
- Publication Type :
- Academic Journal
- Accession number :
- 21439253