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Novel Approaches to Molecular ImagingNovel Approaches to Molecular Imaging Posters |
1 Biomedical Engineering; 2 Dept of Radiology; 3 Dept of Pediatrics; 4 Dept of Medicine; 5 Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia
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Objectives: To evaluate a neutrophil-specific imaging agent in a mouse model of bacterial pneumonia.
Methods: The agent consists of three components: a neutrophil-specific peptide(N-cinnamoyl-F(D)LF(D)LF (cFLFLF)), a biocompatible polymer (76 unit polyethylene glycol, PEG76) to attenuate hepatobiliary and intestinal uptake, and a positron emitter (64Cu). The peptide, cFLFLF, demonstrated high affinity for the neutrophil N-formylpeptide receptor (Kd = 20 nM). Pneumonia was induced in male C57Bl/6 mice by oropharyngeal aspiration of 106 colony forming units of Klebsiella pneumoniae (N=4) or saline for controls (N=4), under anesthesia. At 24 h post infection, cFLFLF-PEG76-64Cu (50-100 µCi in 150-200 µL saline) was injected via the tail vein. MicroPET and respiratory gated microCT imaging were performed 18 h after tracer injection. PET and CT data sets were fused and the CT images were used to guide the placement of the lung regions of interest for standardized uptake value (SUV) measurements. SUVs were measured as the average ROI activity concentration normalized by the injected dose and the weight of the animal.
Results: Lung SUV measurements for infected and control mice 18 h post tracer injection were 0.088±0.016 and 0.060±0.010, respectively (P=0.036).
Conclusions: The tracer exhibited high binding affinity for neutrophils in vitro, which was reflected in vivo by increased uptake in lungs of mice with pneumonia. The peptide is a promising agent for imaging acute neutrophilic inflammation.
Research Support: NIH P01 HL073361
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