ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2012
The synthesis and in vivo pharmacokinetics of fluorinated arachidonic acid: implications for imaging neuroinflammation.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Radiosynthesis of 20-[Prostaglandins, leukotrienes, and essential fatty acids · 2022Article
- Eag1 KOxidative medicine and cellular longevity · 2017Review
- Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.Prostaglandins, leukotrienes, and essential fatty acids · 2015Article
- Pathways of polyunsaturated fatty acid utilization: implications for brain function in neuropsychiatric health and disease.Brain research · 2015Review
- PET and MR imaging of neuroinflammation in hepatic encephalopathy.Metabolic brain disease · 2015Review
- Lithium and the other mood stabilizers effective in bipolar disorder target the rat brain arachidonic acid cascade.ACS chemical neuroscience · 2014Review
- Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma.Progress in lipid research · 2013Review
- Altered fatty acid concentrations in prefrontal cortex of schizophrenic patients.Journal of psychiatric research · 2013Article
- PET radiopharmaceuticals for probing enzymes in the brain.American journal of nuclear medicine and molecular imaging · 2013Article
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9 authors at 5 institutions in 1 country.
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Abstract
unlabelledArachidonic acid (AA) is found in high concentrations in brain phospholipids and is released as a second messenger during neurotransmission and much more so during neuroinflammation and excitotoxicity. Upregulated brain AA metabolism associated with neuroinflammation has been imaged in rodents using [1-(14)C]AA and with PET in Alzheimer disease patients using [1-(11)C]AA. Radiotracer brain AA uptake is independent of cerebral blood flow, making it an ideal tracer despite altered brain functional activity. However, the 20.4-min radioactive half-life of (11)C-AA and challenges of routinely synthesizing (11)C fatty acids limit their translational utility as PET biomarkers.
methodsAs a first step to develop a clinically useful (18)F-fluoroarachidonic acid ((18)F-FAA) with a long radioactive half-life of 109.8 min, we report here a high-yield stereoselective synthetic method of nonradioactive 20-(19)F-FAA. We tested its in vivo pharmacokinetics by infusing purified nonradioactive (19)F-FAA intravenously for 5 min at 2 doses in unanesthetized mice and measured its plasma and brain distribution using gas chromatography-mass spectrometry.
resultsIncorporation coefficients of injected (19)F-FAA into brain phospholipids (ratio of brain (19)F-FAA concentration to plasma input function) were 3- to 29-fold higher for choline glycerophospholipid and phosphatidylinositol than for ethanolamine glycerophospholipid and phosphatidylserine at each of the 2 tested doses. The selectivities and values of incorporation coefficients were comparable to those reported after [1-(14)C]AA (the natural arachidonate) infusion in mice.
conclusionThese results suggest that it would be worthwhile to translate our stereoselective synthetic method for (19)F-FAA to synthesize positron-emitting (18)F-FAA for human brain AA metabolism in neuroinflammatory disorders such as Alzheimer disease.
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