Journal Article

FZJ-2024-03260

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Radiosynthesis and In Vitro Evaluation of [11C]tozadenant as Adenosine A2A Receptor Radioligand

Humpert, S.FZJ* ; Schneider, D.FZJ* ; Lang, M.FZJ* ; Schulze, A.FZJ* ; Neumaier, F.FZJ* ; Holschbach, M.FZJ* ; Bier, D.FZJ* ; Neumaier, B. (Corresponding author)FZJ*

2024
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Please use a persistent id in citations: doi:10.3390/molecules29051089  doi:10.34734/FZJ-2024-03260

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.

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Contributing Institute(s):

1. Nuklearchemie (INM-5)

Research Program(s):

1. 5253 - Neuroimaging (POF4-525) (POF4-525)

Appears in the scientific report 2024

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