These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Effective microPET imaging of brain 5-HT(1A) receptors in rats with [(18) F]MeFWAY by suppression of radioligand defluorination.
    Author: Choi JY, Kim CH, Jeon TJ, Kim BS, Yi CH, Woo KS, Seo YB, Han SJ, Kim KM, Yi DI, Lee M, Kim DG, Kim JY, Lee KC, Choi TH, An G, Ryu YH.
    Journal: Synapse; 2012 Dec; 66(12):1015-23. PubMed ID: 22927318.
    Abstract:
    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.
    [Abstract] [Full Text] [Related] [New Search]