Introduction: [(18) F]MeFWAY has been developed for imaging the serotonin 1A receptors in the brain. The purpose of this study were to verify the metabolic stability of [(18) F]MeFWAY, to measure the degree of defluorination of [(18) F]MeFWAY in vivo, to investigate methods of inhibition of defluorination of [(18) F]MeFWAY, and to assess the efficacy of [(18) F]MeFWAY in rat brains in vivo.
Methods: MicroPET experiments in rats were conducted to confirm the distribution of radioactivity in the brain. Nondisplaceable binding potential (BP(ND) ) in the hippocampus and frontal cortex were also analyzed. Miconazole and fluconazole were tested for the ability to suppress defluorination of [(18) F]MeFWAY. We conducted a blockade and displacement experiment by treating with WAY-100635.
Results: In vitro stability tests showed that MeFWAY was very stable in serum for 6 h, but PET revealed that authentic [(18) F]MeFWAY underwent significant defluorination in vivo. In vitro inhibition study against decreasing parent activity in liver microsomes, miconazole and fluconazole suppressed metabolic elimination of MeFWAY. However, in the PET study, fluconazole showed more potent inhibitory activity than miconazole. In the suppression of metabolizing enzymes using fluconazole, radioactivity in skull was dramatically decreased by 81% (compared with 69% with miconazole) and it was coupled with an increase in brain uptake. Moreover, BP(ND) in hippocampus was 5.53 and 2.66 in frontal cortex. The blockade and displacement study showed the specificity of [(18) F]MeFWAY to 5-HT(1A) receptors.
Conclusion: In the rat brain, [(18) F]MeFWAY microPET showed skull uptake due to defluorination in vivo. We can effectively overcome this drawback with fluconazole.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/syn.21607 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Assessing the applicability of PMOD residence times model for PET image-based radiation dosimetry.
Sci Rep
November 2023
Division of Applied RI, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, Korea.
The effective dose represents the overall internal radiation exposure to the whole body when exposed to radiation sources. This study aims to compare conventional and software-aided methods to derive the effective dose. In the present study, F-T807 and F-Mefway, specific radiotracers for the paired helical tau and serotonin 1A receptor, were administered to healthy subjects (n = 6, each radiotracer), following which whole-body positron emission tomography (PET) images were obtained for 2 h.
View Article and Find Full Text PDFEvidence For Cannabidiol Modulation of Serotonergic Transmission in a Model of Osteoarthritis via PET Imaging and Behavioral Assessment.
Int J Innov Res Med Sci
June 2022
Rodent Behavioral Core, New York University School of Medicine, New York, NY, USA.
Background: Preclinical studies indicate that cannabidiol (CBD), the primary nonaddictive component of cannabis, has a wide range of reported pharmacological effects such as analgesic and anxiolytic actions; however, the exact mechanisms of action for these effects have not been examined in chronic osteoarthritis (OA). Similar to other chronic pain syndromes, OA pain can have a significant affective component characterized by mood changes. Serotonin (5-HT) is a neurotransmitter implicated in pain, depression, and anxiety.
View Article and Find Full Text PDFBiodistribution and Radiation Dosimetry of [F]Mefway in Humans.
Mol Imaging Biol
December 2016
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Purpose: [F]Mefway is a positron emission tomography (PET) radioligand for quantification of the brain serotonin 1A (5-HT) receptor density. The purpose of this study was to evaluate the radiation safety of [F]Mefway in humans.
Procedures: Six healthy volunteers (three males and three females) were whole-body PET scanned for 114 min after injection of [F]Mefway (226 ± 35 MBq).
Comparative assessment of (18) F-Mefway as a serotonin 5-HT1A receptor PET imaging agent across species: Rodents, nonhuman primates, and humans.
J Comp Neurol
May 2016
Department of Medical Physics and Waisman Center, University of Wisconsin, Madison, Wisconsin, 53705.
We have developed (18) F-trans-Mefway ((18) F-Mefway) for positron emission tomography (PET) imaging studies of serotonin 5-HT1A receptors which are implicated in various brain functions. Translation of imaging the 5-HT1A receptor in animal models to humans will facilitate an understanding of the role of the receptor in human brain disorders. We report comparative brain distribution of (18) F-Mefway in normal mice, rats, monkeys, and healthy human volunteers.
View Article and Find Full Text PDFOptimal timing of [¹⁸F]Mefway PET for imaging the serotonin 1A receptor in healthy male subjects.
Appl Radiat Isot
January 2016
Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:
To determine the optimal acquisition time of [(18)F]Mefway PET, we examined the regional specific-to-nonspecific binding ratios and evaluated the relationship between distribution volume ratios (DVRs) and standardized uptake value ratios (SUVRs) in various time windows. The specific-to-nonspecific binding ratios peaked after 40 min and there was a strong correlation between DVR and SUVR in the 60-80 min. Therefore, we recommend the use of a single time point between 60 and 80 min for [(18)F]Mefway static PET.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!