| Reference | 1. Nucl Med Biol. 2000 Jul;27(5):463-6.
<br>
Imaging the 5-HT(1A) receptors with PET: WAY-100635 and analogues.
<br>
Houle S(1), DaSilva JN, Wilson AA.
<br>
Author information: <br>
(1)Vivian M Rakoff PET Centre, Centre for Addiction and Mental Health, Toronto,
Canada. [email protected]
<br>
This paper summarizes our work on WAY-100635 and analogues, labeled either with
carbon-11 or fluorine-18, as potential radioligands for the
5-hydroxytryptamine(1A) (5-HT(1A)) neuroreceptors. Other facets of our work
include: (1) human studies with [O-methyl-(11)C]WAY-100634, the major radioactive
metabolite of [O-methyl-(11)C]WAY-100635, and with [(11)C]CPC 222; (2) use of a
human liver metabolism model to screen in vitro potential metabolic problems in
humans; (3) modification of the “dry method” to prepare
[carbonyl-(11)C]WAY-100635; and (4) validation studies in humans with
[carbonyl-(11)C]WAY-100635.
<br><br>
2. Nucl Med Biol. 2000 Jul;27(5):457-62.
<br>
Fluoro analogs of WAY-100635 with varying pharmacokinetics properties.
<br>
Lang L(1), Jagoda E, Schmall B, Sassaman M, Ma Y, Eckelman WC.
<br>
Author information: <br>
(1)PET Department, Warren G. Magnuson Clinical Center, National Institutes of
Health, Bethesda, MD 20892, USA.
<br>
Radiolabeled derivatives of WAY-100635 have been shown to be important for
imaging in vivo because of their antagonist properties and their specificity for
the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor. Our goal is to prepare a series
of radiofluorinated derivatives of WAY-100635 that, in the rat, range in
pharmacokinetic properties from nearly irreversible to reversible in their
behavior. It appears that derivatives containing a cyclohexanecarboxylic acid
(e.g., FCWAY) with its high affinity and high target to nontarget contrast, has
properties suited to measure receptor concentration. Derivatives based on
phenylcarboxamide (e.g., FBWAY and MeFBAWAY) have properties more suited to the
measurement of changes in endogenous serotonin. The compound containing the
pyrimidine moiety in place of the pyridine moeity in FBWAY (FBWAY 1,3N) appears
to have intermediate properties.
<br><br>
3. Nucl Med Biol. 2000 Jul;27(5):441-7.
<br>
A retrospect on the discovery of WAY-100635 and the prospect for improved
5-HT(1A) receptor PET radioligands.
<br>
Cliffe IA(1).
<br>
Author information: <br>
(1)Department of Chemistry, Vernalis Research, Oakdene Court, 613 Reading Road,
Winnersh, Workingham RG41 5UA, United Kingdom. [email protected]
<br>
Abstract. An outline is given of the developments that led to the identification
of [O-methyl-(11)C]WAY-100635 (4) as the first useful PET ligand for imaging
serotonin(1A) (5-HT(1A)) receptors in the living human brain. Recent attempts to
develop 5-HT(1A) receptor radioligands superior to 4 are reviewed, and
[carbonyl-(11)C]WAY-100635 (6) has been shown to be the best currently available
radioligand for human studies. Of other (11)C-radiolabelled compounds,
[O-methyl-(11)C](R,S)-CPC-222 (9), DWAY (8), and [(11)C]NAD-299 (14) all
demonstrate specific binding to 5-HT(1A) receptors in animals and warrant further
expedited studies in humans. The trans-fluorocyclohexane, 12, and fluorobenzene,
[(18)F]p-MPPF 13, are highlighted as examples of promising (18)F-labelled
ligands.
<br>
|
