Development of matrix metalloproteinase-targeted probes for lung inflammation detection with positron emission tomography View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Naoya Kondo, Takashi Temma, Kazuki Aita, Saeka Shimochi, Kazuhiro Koshino, Michio Senda, Hidehiro Iida

ABSTRACT

As matrix metalloproteinases (MMPs), especially MMP-9 and MMP-12 are involved in the pathological processes associated with chronic obstructive pulmonary disease (COPD), we developed a novel radiofluorinated probe, 18F-IPFP, for MMPs-targeted positron emission tomography (PET). 18F-IPFP was designed by iodination of MMP inhibitor to enhance the affinity, and labelled with a compact prosthetic agent, 4-nitrophenyl 2-18F-fluoropropionate (18F-NFP). As a result, IPFP demonstrated the highest affinity toward MMP-12 (IC50 = 1.5 nM) among existing PET probes. A COPD model was employed by exposing mice to cigarette smoke and the expression levels of MMP-9 and MMP-12 were significantly increased in the lungs. Radioactivity accumulation in the lungs 90 min after administration of 18F-IPFP was 4× higher in COPD mice than normal mice, and 10× higher than in the heart, muscle, and blood. Ex vivo PET confirmed the radioactivity distribution in the tissues and autoradiography analysis demonstrated that accumulation differences in the lungs of COPD mice were 2× higher than those of normal mice. These results suggest that 18F-IPFP is a promising probe for pulmonary imaging and expected to be applied to various MMP-related diseases for early diagnosis, tracking of therapeutic effects, and new drug development in both preclinical and clinical applications. More... »

PAGES

1347

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-19890-1

DOI

http://dx.doi.org/10.1038/s41598-018-19890-1

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https://app.dimensions.ai/details/publication/pub.1100427080

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29358724


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