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词条 Mefway (18F)
释义

  1. Chemistry

  2. Animal PET studies

  3. Human PET studies

  4. References

{{DISPLAYTITLE:Mefway (18F)}}{{drugbox
| drug_name = Mefway (18F)
| image = Mefway 18F skeletal.svg
| IUPAC_name = 4-[(18F)fluoromethyl]-N2-[4-(2-methoxyphenyl)piperazin-1-yl]ethylN-(pyridin-2-yl)cyclohexane-1-carboxamide
| synonyms =
| CAS_number = 943962-60-5
| PubChem= 11963740
| ChemSpiderID = 10137857
| ATC_prefix = none
| smiles = COC1=CC=CC=C1N2CCN(CC2)CCN(C3=CC=CC=N3)C(=O)C4CCC(CC4)C[18F]
| C=26 | H=35 | F=1 | N=4 | O=2
| molecular_weight = 453.583 g/mol
| StdInChI=1S/C26H35FN4O2/c1-33-24-7-3-2-6-23(24)30-17-14-29(15-18-30)16-19-31(25-8-4-5-13-28-25)26(32)22-11-9-21(20-27)10-12-22/h2-8,13,21-22H,9-12,14-20H2,1H3/i27-1
| StdInChIKey = BQGLPDFQLBNUGU-FMLNDMEQSA-N
| pregnancy_category = N/A
| legal_status = Research compound
}}Mefway is a serotonin 5-HT1A receptor antagonist used in medical research, usually in the form of mefway (18F) as a positron emission tomography (PET) radiotracer.[1]

Chemistry

Mefway is closely related to the research compound WAY-100,635. The compound adds a fluoromethyl group to the cyclohexyl ring of WAY-100,635 and it is effectively prepared with automation module.[2]

There are two isomers with regard to the cyclohexane ring, of which the trans conformation has the higher 5-HT1A specificity.[3]

Animal PET studies

In one study the uptake and retention of mefway (18F) was found to be similar to that found for 11C-WAY-100,635. Head-to-head comparison of mefway (18F) and 11C-WAY-100,635 have been evaluated. Since 11C-WAY-100,635 is the current ‘gold standard’ and difficult to synthesize, a suitable fluorine-18 replacement as in mefway is highly desired.[4] In addition, mefway (18F) showed comparable brain uptake and the target-to-reference ratios compared to fcway(18F)[5]

The ability to separately measure dissociation constant, KD and receptor density Bmax has been shown to be of potential value rather than simply comparing binding potential, BPND. Multiple injection mefway PET experiments can be used for the in-vivo measurement of 5-HT1A receptor density.[6]

Imaging studies of mefway on in vivo and ex vivo rat brains indicate that the substance binds to the known 5-HT1A receptor regions including the dorsal raphe. These findings support that the dorsal raphe is measurable in rat PET studies.[7] Mefway (18F) undergoes in vivo defluorination in rodent brain and this phenomenon was effectively suppressed by cytochrome P450 inhibitor (i.e. fluconazole).[8] Animal models of Parkinson's disease and the acute physical stress model exhibited significant decrement of binding potential in the hippocampus [9][10]

Human PET studies

First-in-human studies have shown in vivo stability of mefway (18F) and its localization to 5-HT1A receptor-rich regions in the human brain, including the raphe nucleus.[11] Mefway (18F) is highly selective for the human serotonin 5-HT1A receptor and may therefore may be used to quantify serotonin 5-HT1A receptor distribution in brain regions for the study of various central nervous system disorders.[12]

References

1. ^{{Cite journal| last1 = Saigal | first1 = N.| last2 = Pichika | first2 = R.| last3 = Easwaramoorthy | first3 = B.| last4 = Collins | first4 = D.| last5 = Christian | first5 = B. T.| last6 = Shi | first6 = B.| last7 = Narayanan | first7 = T. K.| last8 = Potkin | first8 = S. G.| last9 = Mukherjee | first9 = J.| title = Synthesis and biologic evaluation of a novel serotonin 5-HT1A receptor radioligand, 18F-labeled mefway, in rodents and imaging by PET in a nonhuman primate| journal = Journal of Nuclear Medicine| volume = 47| issue = 10| pages = 1697–1706| year = 2006| pmid = 17015907}}
2. ^{{cite journal|last1=Choi|first1=JY|last2=Kim|first2=CH|last3=Ryu|first3=YH|last4=Seo|first4=YB|last5=Truong|first5=P|last6=Kim|first6=EJ|last7=Choi|first7=TH|last8=Kang|first8=J|last9=Lee|first9=M|last10=Kim|first10=DG|last11=Lee|first11=JD|last12=Jeon|first12=TJ|title=Optimization of the radiosynthesis of [18F]MEFWAY for imaging brain serotonin 1A receptors by using the GE TracerLab FXFN-Pro module.|journal=Journal of Labelled Compounds & Radiopharmaceuticals|date= 2013|volume=56|issue=12|pages=589–94|pmid=24285234|doi=10.1002/jlcr.3067}}
3. ^{{Cite journal| last1 = Wooten | first1 = D.| last2 = Hillmer | first2 = A.| last3 = Murali | first3 = D.| last4 = Barnhart | first4 = T.| last5 = Schneider | first5 = M. L.| last6 = Mukherjee | first6 = J.| last7 = Christian | first7 = B. T.| doi = 10.1016/j.nucmedbio.2011.04.001| title = An in vivo comparison of cis- and trans-[18F]mefway in the nonhuman primate| journal = Nuclear Medicine and Biology| year = 2011| pmid = 21741252| pmc = 3190069| volume=38 | issue=7 | pages=925–32}}
4. ^{{Cite journal| last1 = Wooten | first1 = D. W.| last2 = Moraino | first2 = J. D.| last3 = Hillmer | first3 = A. T.| last4 = Engle | first4 = J. W.| last5 = Dejesus | first5 = O. J.| last6 = Murali | first6 = D.| last7 = Barnhart | first7 = T. E.| last8 = Nickles | first8 = R. J.| last9 = Davidson | first9 = R. J.| last10 = Schneider| doi = 10.1002/syn.20878 | first10 = M. L.| last11 = Mukherjee | first11 = J.| last12 = Christian | first12 = B. T.| title = In vivo kinetics of \\F-18]MEFWAY: A comparison with \\C-11]WAY100635 and \\F-18]MPPF in the nonhuman primate| journal = Synapse| volume = 65| issue = 7| pages = 592–600| year = 2011| pmid = 21484878| pmc =3080024}}
5. ^{{cite journal|last1=Choi|first1=JY|last2=Kim|first2=BS|last3=Kim|first3=CH|last4=Kim|first4=DG|last5=Han|first5=SJ|last6=Lee|first6=K|last7=Kim|first7=KM|last8=An|first8=G|last9=Choi|first9=TH|last10=Yoo|first10=SD|last11=Ryu|first11=YH|title=Translational possibility of [18 F]Mefway to image serotonin 1A receptors in humans: Comparison with [18 F]FCWAY in rodents|journal=Synapse|date=2014|volume=68|issue=12|pages=595–603|pmid=25056144|doi=10.1002/syn.21771}}
6. ^{{Cite journal| last1 = Wooten | first1 = D. W.| last2 = Hillmer | first2 = A. T.| last3 = Moirano | first3 = J. M.| last4 = Ahlers | first4 = E. O.| last5 = Slesarev | first5 = M.| last6 = Barnhart | first6 = T. E.| last7 = Mukherjee | first7 = J.| last8 = Schneider | first8 = M. L.| last9 = Christian | first9 = B. T.| doi = 10.1038/jcbfm.2012.43| title = Measurement of 5-HT1A receptor density and in-vivo binding parameters of \\18F]mefway in the nonhuman primate| journal = Journal of Cerebral Blood Flow & Metabolism| volume = 32| issue = 8| pages = 1546–1558| year = 2012| pmid = 22472611| pmc =3421091}}
7. ^{{Cite journal| last1 = Saigal | first1 = N.| last2 = Bajwa | first2 = A. K.| last3 = Faheem | first3 = S. S.| last4 = Coleman | first4 = R. A.| last5 = Pandey | first5 = S. K.| last6 = Constantinescu | first6 = C. C.| last7 = Fong | first7 = V.| last8 = Mukherjee | first8 = J.| title = Evaluation of serotonin 5-HT1Areceptors in rodent models using \\18F]mefway PET| doi = 10.1002/syn.21665| journal = Synapse| volume = 67| issue = 9| pages = 596–608| year = 2013| pmid = 23504990| pmc =3744326}}
8. ^{{cite journal|last1=Choi|first1=JY|last2=Kim|first2=CH|last3=Jeon|first3=TJ|last4=Kim|first4=BS|last5=Yi|first5=CH|last6=Woo|first6=KS|last7=Seo|first7=YB|last8=Han|first8=SJ|last9=Kim|first9=KM|last10=Yi|first10=DI|last11=Lee|first11=M|last12=Kim|first12=DG|last13=Kim|first13=JY|last14=Lee|first14=KC|last15=Choi|first15=TH|last16=An|first16=G|last17=Ryu|first17=YH|title=Effective microPET imaging of brain 5-HT(1A) receptors in rats with [(18) F]MeFWAY by suppression of radioligand defluorination|journal=Synapse|date=December 2012|volume=66|issue=12|pages=1015–23|pmid=22927318|doi=10.1002/syn.21607}}
9. ^{{Cite journal | pmid = 25064461| year = 2014| author1 = Lee| first1 = M| title = Dopaminergic neuron destruction reduces hippocampal serotonin 1A receptor uptake of trans-(18)FMefway| journal = Applied Radiation and Isotopes| volume = 94| pages = 30–4| last2 = Ryu| first2 = Y. H.| last3 = Cho| first3 = W. G.| last4 = Jeon| first4 = T. J.| last5 = Lyoo| first5 = C. H.| last6 = Kang| first6 = Y. W.| last7 = Lee| first7 = S. J.| last8 = Kim| first8 = C. H.| last9 = Kim| first9 = D. G.| last10 = Kang| first10 = J. H.| last11 = Seo| first11 = Y. B.| last12 = Yi| first12 = C. H.| last13 = Lee| first13 = K| last14 = Choi| first14 = T. H.| last15 = Choi| first15 = J. Y.| doi = 10.1016/j.apradiso.2014.06.016}}
10. ^{{Cite journal | pmid = 24771590| year = 2014| author1 = Choi| first1 = J. Y.| title = Acute physical stress induces the alteration of the serotonin 1A receptor density in the hippocampus| journal = Synapse| volume = 68| issue = 8| pages = 363–8| last2 = Shin| first2 = S| last3 = Lee| first3 = M| last4 = Jeon| first4 = T. J.| last5 = Seo| first5 = Y| last6 = Kim| first6 = C. H.| last7 = Kim| first7 = D. G.| last8 = Yi| first8 = C. H.| last9 = Lee| first9 = K| last10 = Choi| first10 = T. H.| last11 = Kang| first11 = J. H.| last12 = Ryu| first12 = Y. H.| doi = 10.1002/syn.21748}}
11. ^{{Cite journal | pmid = 25453045| year = 2014| author1 = Hillmer| first1 = A. T.| title = First-in-Human Evaluation of 18F-Mefway, a PET Radioligand Specific to Serotonin-1A Receptors| journal = Journal of Nuclear Medicine| volume = 55| issue = 12| pages = 1973–9| last2 = Wooten| first2 = D. W.| last3 = Bajwa| first3 = A. K.| last4 = Higgins| first4 = A. T.| last5 = Lao| first5 = P. J.| last6 = Betthauser| first6 = T. J.| last7 = Barnhart| first7 = T. E.| last8 = Rowley| first8 = H. A.| last9 = Stone| first9 = C. K.| last10 = Johnson| first10 = S. C.| last11 = Mukherjee| first11 = J| last12 = Christian| first12 = B. T.| doi = 10.2967/jnumed.114.145151 | pmc=4316674}}
12. ^{{Cite journal | pmid = 26509362| pmc = 4783179| year = 2015| author1 = Mukherjee| first1 = J| title = Comparative assessment of 18 F-Mefway as a serotonin 5-HT1A receptor PET imaging agent across species- rodents, nonhuman primates, and humans| journal = Journal of Comparative Neurology| volume = 524| issue = 7| pages = 1457–71| last2 = Bajwa| first2 = A. K.| last3 = Wooten| first3 = D. W.| last4 = Hillmer| first4 = A. T.| last5 = Pan| first5 = M. L.| last6 = Pandey| first6 = S. K.| last7 = Saigal| first7 = N| last8 = Christian| first8 = B. T.| doi = 10.1002/cne.23919}}
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