Imaging 5-HT1A receptors with positron emission tomography

Two C-Methyl Derivatives of [11C]WAY-100635 – Effects of an Amido α-Methyl Group on Metabolism and Brain 5-HT1A Receptor Radioligand Behavior in Monkey*

“…AM250 (200.13 MHz) instrument. 13 C NMR spectra were obtained at 300 K in CDCl 3 on a Varian Gemini (50 MHz) instrument or in CD 3 CN on a Bruker AM250 (62.9 MHz) instrument. Chemical shifts are reported in d values (ppm), by reference to the hydrogenated residues of deuteriated solvent as internal standard.…”

“…A structural analogue of WAY-100635 known as CPC-222 (2), where the cyclohexyl group has been replaced by the bulkier 2-bicyclo [2,2,2]octanyl group, has been labeled with carbon-11 and shown to resist amide hydrolysis in human liver microsomes in vitro [11,12] and in human subjects [12,13]. CPC-222 is an antagonist like WAY-100635 [14].…”

Synthesis and Biodistribution of (R,S)-[O-Methyl-11C]-1-[3-(5-Methoxy-1,2,3,4-tetrahydro-1-naphtalenyl)propyl]-4-Phenylpiperazine (PNU-157760), A Putative Radioligand for 5-HT1AReceptors

“…Analysis of arterial plasma in monkey showed that only 20% of radioactivity remained as the parent compound at 30 min postinjection (25) It was shown by in vitro metabolic assay with human liver cytosol and microsomal preparations that metabolically stable analogues of WAY-100635 pertaining high affinity for the serotonin receptor could be obtained by the substitution of cyclohexyl moiety for the bicycloalkyl group (16). Recently images of the 5-HT 1A receptorrich areas in the living human brain were obtained with [O-methyl- 11 C]CPC-222 (27). No decarbonylation metabolite, [O-methyl- 11 C]WAY-100634, was found in the plasma of healthy volunteers and a good brain penetration with the peak cortical concentration corresponding to 2% of the injected dose was reported.…”

“…11 C]WAY) (13,27). This disappointing result could be explained partially by the higher lipophilicity of the CPC-222, calculated logP ϭ 5.3, and its lower affinity for the serotonin receptor, IC 50 ϭ 8.1 nM versus [ 3 H]8-OH-DPAT on rat hippocampal homogenates, as compared to WAY-100635, IC 50 ϭ 6.0 nM and logP ϭ 4.7 (16).…”

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

“…Cohen et al 2000 [57] Opioid receptor: unselective [ 18 F]fl uorethyldiprenorphine Baumgärtner et al 2006 [58] Neuropeptide [60] Serotonin receptor: 5-HT 1A [carbonyl- 11 C]WAY-100635 Parsey et al 2000 [61] Serotonin receptor: 5-HT 1A [carbonyl-11 C]DWAY Andree et al 2002 [62] Serotonin receptor: 5-HT 1A [ 11 C]CPC- 222 Houle et al 1997 [63] Serotonin receptor: 5-HT 1A [ 11 C]CUMI- 101 Milak et al 2010 [64] Serotonin receptor: [66] Serotonin receptor: 5-HT 1B [ 11 C]P943 Gallezot et al 2010 [67] Serotonin receptor: 5-HT 1B [ 11 C]AZ10419369 Varnäs et al 2011 [68] Serotonin receptor: 5-HT 1B [ 11 C]P943 Murrough et al 2011 [69] Serotonin receptor: 5-HT 2A [ 11 C]MDL100907 Hinz et al 2007 [70] Serotonin receptor: 5-HT 2A [ 18 F]altanserin Rosier et al 1996 [71] Serotonin receptor: 5-HT 2A [ 18 F]deuteroaltanserin Van Dyck et al 2000 [72] Serotonin receptor: 5-HT 2A [ 18 F]setoperone Trichard et al 1998 [73] Serotonin receptor: 5-HT 2A [ 18 F]Cimbi-36 Ettrup et al 2014 [74] Serotonin receptor: 5-HT 4 [ 11 C]SB207145 Marner et al 2009 [75] Serotonin receptor: 5-HT 6 [ 11 C]GSK215083 Parker et al 2012 [76] Sigma receptor: σ 1 [ 11 C]SA4503 Mishina et al 2005 [77] Sigma receptor: σ 1 [ 18 F]FPS Waterhouse et al 2004 [78] Translocator protein (TSPO) b [ 11 C]PK11195 Junck et al 1989 [79] Translocator protein (TSPO) (R)-[ 11 C]PK11195 Banati et al 1999 [80] Translocator protein (TSPO) [ 11 C]PBR28 Brown et al 2007 [81] Translocat...…”