Development of radioligands with optimized imaging properties for quantification of nicotinic acetylcholine receptors by positron emission tomography.
OBJECTIVE
There is an urgent need for positron emission tomography (PET) imaging of the nicotinic acetylcholine receptors (nAChR) to study the role of the nicotinic system in Alzheimer's and Parkinson's diseases, schizophrenia, drug dependence and many other disorders. Greater understanding of the underlying mechanisms of the nicotinic system could direct the development of medications to treat these disorders. Central nAChRs also contribute to a variety of brain functions, including cognition, behavior and memory.


METHODS
Currently, only two radiotracers, (S)-3-(azetidin-2-ylmethoxy)-2-[(18)F]fluoropyridine (2-[(18)F]FA) and (S)-5-(azetidin-2-ylmethoxy)-2-[(18)F]fluoropyridine (6-[(18)F]FA), are available for studying nAChRs in human brain using PET. However, the "slow" brain kinetics of these radiotracers hamper mathematical modeling and reliable measurement of kinetic parameters since it takes 4-7 h of PET scanning for the tracers to reach steady state. The imaging drawbacks of the presently available nAChR radioligands have initiated the development of radioligands with faster brain kinetics by several research groups.


RESULTS
This minireview attempts to survey the important achievements of several research groups in the discovery of PET nicotinic radioligands reached recently. Specifically, this article reviews papers published from 2006 through 2008 describing the development of fifteen new nAChR (11)C-and (18)F-ligands that show improved imaging properties over 2-[(18)F]FA.


CONCLUSIONS
The continuous efforts of radiomedicinal chemists led to the development of several interesting PET radioligands for imaging of nAChR including [(18)F]AZAN, a potentially superior alternative to 2-[(18)F]FA.
Horti
Andrew G
AG
Division of Nuclear Medicine, Department of Radiology, Johns Hopkins University, Baltimore, Maryland, United States. ahorti1@jhmi.edu
Gao
Yongjun
Y
Kuwabara
Hiroto
H
Dannals
Robert F
RF
D000818:Animals; D001921:Brain / Q000378:metabolism; D002247:Carbon Isotopes / Q000737:chemistry; D015195:Drug Design; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008962:Models, Theoretical; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*
D002247:Carbon Isotopes; D005462:Fluorine Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic