Abstract
We report herein the discovery of a positron emission tomography (PET) tracer for the (NOD)-like receptor protein 3 (NLRP3). Our recent medicinal chemistry campaign on developing sulfonamide-based NLRP3 inhibitors led to an analog, 1, with a methoxy substituent amenable to labeling with carbon-11. PET/CT imaging studies indicated that [11C]1 exhibited rapid blood-brain barrier (BBB) penetration and moderate brain uptake, as well as blockable uptake in the brain. [11C]1, thus suggesting the potential to serve as a useful tool for imaging NLRP3 inflammasome in living brains.
Keywords:
Blockable uptake; Blood-brain barrier (BBB) penetration; NLRP3; Positron emission tomography (PET); Sulfonamide derivative.
Copyright © 2021 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood-Brain Barrier / metabolism
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Carbon Radioisotopes
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Drug Discovery*
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Inflammasomes / analysis*
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Inflammasomes / metabolism
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Mice
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Mice, Inbred C57BL
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Molecular Structure
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NLR Family, Pyrin Domain-Containing 3 Protein / analysis*
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NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
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Positron Emission Tomography Computed Tomography*
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Radiopharmaceuticals / chemical synthesis
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Radiopharmaceuticals / chemistry*
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Radiopharmaceuticals / metabolism
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Sulfonamides / chemical synthesis
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Sulfonamides / chemistry*
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Sulfonamides / metabolism
Substances
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Carbon Radioisotopes
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Carbon-11
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Inflammasomes
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NLR Family, Pyrin Domain-Containing 3 Protein
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Nlrp3 protein, mouse
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Radiopharmaceuticals
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Sulfonamides