ArticleNuclear medicine and biology2013
Synthesis and preclinical evaluation of [11C-carbonyl]PF-04457845 for neuroimaging of fatty acid amide hydrolase.
Article in Nuclear medicine and biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- PET Molecular Imaging of the Endocannabinoid System in Psychiatric Disorders.Neuroscience bulletin · 2026Review
- Positron Emission Tomography Imaging of the Endocannabinoid System: Opportunities and Challenges in Radiotracer Development.Journal of medicinal chemistry · 2021Review
- "In-loop" [Journal of labelled compounds & radiopharmaceuticals · 2018Article
- New methodologies for the preparation of carbon-11 labeled radiopharmaceuticals.Clinical and translational imaging · 2017Review
- (11)C[double bond, length as m-dash]O bonds made easily for positron emission tomography radiopharmaceuticals.Chemical Society reviews · 2016Review
- Synthesis of Diverse (11)C-Labeled PET Radiotracers via Direct Incorporation of [(11)C]CO2.Bioconjugate chemistry · 2016Article
- Synthesis and Preliminary PET Imaging Studies of a FAAH Radiotracer ([¹¹C]MPPO) Based on α-Ketoheterocyclic Scaffold.ACS chemical neuroscience · 2016Article
- Synthesis and Preclinical Evaluation of Sulfonamido-based [(11)C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase.Theranostics · 2016Article
- Synthesis and preclinical evaluation of [¹⁸F]FCHC for neuroimaging of fatty acid amide hydrolase.Molecular imaging and biology · 2015Article
- PET imaging of fatty acid amide hydrolase with [(18)F]DOPP in nonhuman primates.Molecular pharmaceutics · 2014Article
- Radiosynthesis and ex vivo evaluation of [(11)C-carbonyl]carbamate- and urea-based monoacylglycerol lipase inhibitors.Nuclear medicine and biology · 2014Article
- A systems pharmacology perspective on the clinical development of Fatty Acid amide hydrolase inhibitors for pain.CPT: pharmacometrics & systems pharmacology · 2014Article
- Development and characterization of a promising fluorine-18 labelled radiopharmaceutical for in vivo imaging of fatty acid amide hydrolase.Bioorganic & medicinal chemistry · 2013Article
- 11CO2 fixation: a renaissance in PET radiochemistry.Chemical communications (Cambridge, England) · 2013Review
- Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT.Molecular imagingReview
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionFatty acid amide hydrolase (FAAH) has a significant role in regulating endocannabinoid signaling in the central nervous system. As such, FAAH inhibitors are being actively sought for pain, addiction, and other indications. This has led to the recent pursuit of positron emission tomography (PET) radiotracers targeting FAAH. We report herein the preparation and preclinical evaluation of [(11)C-carbonyl]PF-04457845, an isotopologue of the potent irreversible FAAH inhibitor.
methodsPF-04457845 was radiolabeled at the carbonyl position via automated [(11)C]CO(2)-fixation. Ex vivo brain biodistribution of [(11)C-carbonyl]PF-04457845 was carried out in conscious rats. Specificity was determined by pre-administration of PF-04457845 or URB597 prior to [(11)C-carbonyl]PF-04457845. In a separate experiment, rats injected with the title radiotracer had whole brains excised, homogenized and extracted to examine irreversible binding to brain parenchyma.
resultsThe title compound was prepared in 5 ± 1% (n = 4) isolated radiochemical yield based on starting [(11)C]CO(2) (decay uncorrected) within 25 min from end-of-bombardment in >98% radiochemical purity and a specific activity of 73.5 ± 8.2 GBq/μmol at end-of-synthesis. Uptake of [(11)C-carbonyl]PF-04457845 into the rat brain was high (range of 1.2-4.4 SUV), heterogeneous, and in accordance with reported FAAH distribution. Saturable binding was demonstrated by a dose-dependent reduction in brain radioactivity uptake following pre-treatment with PF-04457845. Pre-treatment with the prototypical FAAH inhibitor, URB597, reduced the brain radiotracer uptake in all regions by 71-81%, demonstrating specificity for FAAH. The binding of [(11)C-carbonyl]PF-04457845 to FAAH at 40 min post injection was irreversible as 98% of the radioactivity in the brain could not be extracted.
conclusions[(11)C-carbonyl]PF-04457845 was rapidly synthesized via an automated radiosynthesis. Ex vivo biodistribution studies in conscious rodents demonstrate that [11C PF-04457845 is a promising candidate radiotracer for imaging FAAH in the brain with PET. These results coupled with the known pharmacology and toxicology of PF-04457845 should facilitate clinical translation of this radiotracer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.