RT Journal Article
SR Electronic
T1 Molecular Imaging of Heparan Sulfate Expression with Radiolabeled Recombinant Eosinophil Cationic Protein Predicts Allergic Lung Inflammation in a Mouse Model for Asthma
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 793
OP 800
DO 10.2967/jnumed.112.111393
VO 54
IS 5
A1 Hui-Chen Chen
A1 Hao-Teng Chang
A1 Po-Han Huang
A1 Margaret Dah-Tsyr Chang
A1 Ren-Shyan Liu
A1 Yu-Jung Lin
A1 Chia-Hung Hsieh
YR 2013
UL http://jnm.snmjournals.org/content/54/5/793.abstract
AB Heparan sulfate proteoglycans (HSPGs) are glycoproteins consisting of a core protein to which linear heparan sulfate (HS) side chains are covalently attached. These HS side chains mediate a variety of biologic functions involved in inflammation. Radionuclide imaging of HS side chains in tissues with inflammation may be used for the stratification of patients who would most likely benefit from HSPG-targeting therapy. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of HS side chain expression in a mouse model of asthma using the recombinant eosinophil cationic protein (rECP). Methods: rECP was radioiodinated with 125I or 123I using the Chloramine-T method. The 50% inhibitory concentration value for 125I-labeled rECP was determined in a competitive cell-binding assay using Beas-2B cells. The binding of radiolabeled rECP to HS side chains was evaluated both in vitro and in vivo. The biodistribution of radiolabeled rECP was assessed in asthma mice or in control mice using SPECT imaging, ex vivo biodistribution measurements, and microautoradiography. Results: The 50% inhibitory concentration value for 125I-rECP was 7.4 ± 0.1 nM. The loss of HS side chains substantially inhibited the cellular and tissue uptake of 125I- or 123I-rECP, indicating that HS side chains of HSPGs are required for 125I- or 123I-eosinophil cationic protein binding and uptake both in vitro and in vivo. SPECT imaging demonstrated an appreciably higher accumulation of radioactivity in the lungs of asthma mice than in those of control mice. Ex vivo biodistribution studies also confirmed that there was at least a 4-fold increase in the lung-to-muscle ratio of asthma mice, compared with control mice. The accumulation of radiolabeled rECP was linearly correlated with leukocyte infiltration. Conclusion: This study illustrates the feasibility of using radiolabeled rECP for the visualization of HS side chains of HSPGs and the evaluation of allergic lung inflammation in living subjects. Our data indicate that radiolabeled rECP is a novel imaging agent for HS side chains of HSPGs in predicting allergic lung inflammation in living mice.