Abstract：
:The histamine H(3) receptor (H(3)R) plays a role in cognition and memory processes and is implicated in different neurological disorders, including Alzheimer's disease, schizophrenia, and narcolepsy. In vivo studies of the H(3)R occupancy using a radiolabeled PET tracer would be very useful for CNS drug discovery and development. We report here the radiosynthesis, in vitro and in vivo evaluation of a novel (18)F-labeled high-affinity H(3)R antagonist (18)F-ST889. The radiosynthesis was accomplished via nucleophilic substitution of the mesylate leaving group with a radiochemical yield of 8-20%, radiochemical purity >99%, and specific radioactivity > 65 GBq/μmol. (18)F-ST889 exhibited high in vivo stability and rather low lipophilicity (logD(7.4)=0.35 ± 0.09). In vitro autoradiography showed specific binding in H(3)R-rich brain regions such as striatum and cortex. However, in vivo PET imaging of the rat brain with (18)F-ST889 was not successful. Possible reasons are discussed.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Selivanova SV,Honer M,Combe F,Isensee K,Stark H,Krämer SD,Schubiger PA,Ametamey SMdoi
10.1016/j.bmc.2012.03.024subject
Has Abstractpub_date
2012-05-01 00:00:00pages
2889-96issue
9eissn
0968-0896issn
1464-3391pii
S0968-0896(12)00214-3journal_volume
20pub_type
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