An activatable PET imaging radioprobe is a dynamic reporter of myeloperoxidase activity in vivo
| Autor: | Gregory R. Wojtkiewicz, John W. Chen, Negin Jalali Motlagh, Cuihua Wang, Kevin P. Maresca, Edmund J. Keliher, Matthias W.G. Zeller, Matthias Nahrendorf, Hye-Yeong Kim, Jianqing Chen, Maaz S. Ahmed, Aaron D. Aguirre, Leonard Buckbinder |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Fluorine Radioisotopes animal diseases Myocardial Infarction Inflammation Pharmacology Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine Non-competitive inhibition In vivo medicine Animals Humans Cytotoxicity Peroxidase chemistry.chemical_classification Multidisciplinary biology Chemistry Radiosynthesis Biological Sciences Mice Inbred C57BL 030104 developmental biology Enzyme Myeloperoxidase Positron-Emission Tomography biology.protein Female medicine.symptom 030217 neurology & neurosurgery |
| Popis: | Myeloperoxidase (MPO) is a critical proinflammatory enzyme implicated in cardiovascular, neurological, and rheumatological diseases. Emerging therapies targeting inflammation have raised interest in tracking MPO activity in patients. We describe 18 F-MAPP, an activatable MPO activity radioprobe for positron emission tomography (PET) imaging. The activated radioprobe binds to proteins and accumulates at sites of MPO activity. The radioprobe 18 F-MAPP has a short blood half-life, remains stable in plasma, does not demonstrate cytotoxicity, and crosses the intact blood–brain barrier. The 18 F-MAPP imaging detected sites of elevated MPO activity in living mice embedded with human MPO and in mice induced with chemical inflammation or myocardial infarction. The 18 F-MAPP PET imaging noninvasively differentiated varying amounts of MPO activity, competitive inhibition, and MPO deficiency in living animals, confirming specificity and showing that the radioprobe can quantify changes in in vivo MPO activity. The radiosynthesis has been optimized and automated, an important step in translation. These data indicate that 18 F-MAPP is a promising translational candidate to noninvasively monitor MPO activity and inflammation in patients. |
| Databáze: | OpenAIRE |
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