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@ARTICLE{Humpert:1026004,
author = {Humpert, Swen and Schneider, Daniela and Lang, Markus and
Schulze, Annette and Neumaier, Felix and Holschbach, Marcus
and Bier, Dirk and Neumaier, Bernd},
title = {{R}adiosynthesis and {I}n {V}itro {E}valuation of
[11{C}]tozadenant as {A}denosine {A}2{A} {R}eceptor
{R}adioligand},
journal = {Molecules},
volume = {29},
number = {5},
issn = {1420-3049},
address = {Basel},
publisher = {MDPI},
reportid = {FZJ-2024-03260},
pages = {1089},
year = {2024},
abstract = {Tozadenant
(4-hydroxy-N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide)
is a highly selective adenosine A2A receptor (A2AR)
antagonist and a promisinglead structure for the development
of A2AR-selective positron emission tomography (PET)
probes.Although several 18F-labelled tozadenant derivatives
showed favorable in vitro properties, recentin vivo PET
studies observed poor brain penetration and lower specific
binding than anticipated fromthe in vitro data. While these
findings might be attributable to the structural
modification associatedwith 18F-labelling, they could also
reflect inherent properties of the parent compound.
However,PET studies with radioisotopologues of tozadenant to
evaluate its cerebral pharmacokinetics andbrain distribution
are still lacking. In the present work, we applied
N-Boc-O-desmethyltozadenantas a suitable precursor for the
preparation of [O-methyl-11C]tozadenant ([11C]tozadenant) by
Omethylationwith [11C]methyl iodide followed by acidic
deprotection. This approach afforded[11C]tozadenant in
radiochemical yields of 18 ± $2\%,$ with molar activities
of 50–60 GBq/μmol(1300–1600 mCi/μmol) and
radiochemical purities of 95 ± $3\%.$ In addition, in vitro
autoradiographyin pig and rat brain slices demonstrated the
expected striatal accumulation pattern and confirmedthe A2AR
specificity of the radioligand, making it a promising tool
for in vivo PET studies on thecerebral pharmacokinetics and
brain distribution of tozadenant.},
cin = {INM-5},
ddc = {540},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {5253 - Neuroimaging (POF4-525)},
pid = {G:(DE-HGF)POF4-5253},
typ = {PUB:(DE-HGF)16},
pubmed = {38474602},
UT = {WOS:001183457000001},
doi = {10.3390/molecules29051089},
url = {https://juser.fz-juelich.de/record/1026004},
}