In vivo biodistribution of two [18F]-labelled muscarinic cholinergic receptor ligands: 2-[18F]- and 4-[18F]-fluorodexetimide.
Two [18F]-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-[18F]- or 4-[18F]-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies.
Wilson
A A
AA
Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2179.
Scheffel
U A
UA
Dannals
R F
RF
Stathis
M
M
Ravert
H T
HT
Wagner
H N
HN
D000818:Animals; D001285:Atropine / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003909:Dexetimide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods*
D011976:Receptors, Muscarinic; C067992:2-fluorodexetimide; C067994:4-fluorodexetimide; D003909:Dexetimide; D001285:Atropine