Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11C]WAY-100635

Pike, Victor W.; McCarron, Julie A.; Lammertsma, Adriaan A.; Osman, Safiye; Hume, Susan P.; Sargent, Peter A.; Bench, C. J.; Cliffe, Ian A.; Fletcher, A; Grasby, Paul M.

doi:10.1016/0014-2999(96)00079-9

Cited by 206 publications

(99 citation statements)

References 3 publications

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“…To date, WAY 100635 and its analogues have been the most used radiotracers for in vivo labeling of 5-HT 1A receptors (Pike et al 1996;Farde et al 1997;Carson et al 2000). [ 3 H]WAY 100635 has a moderate affinity for 5-HT 1A and in the present study showed partial reversibility in its binding kinetics to receptors in the frontal cortex and hippocampus.…”

Section: Discussionmentioning

confidence: 58%

Effects of Endogenous Neurotransmitters on the in vivo Binding of Dopamine and 5-HT Radiotracers in Mice

Rice

2001

Neuropsychopharmacology

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Section: Discussionmentioning

confidence: 58%

Effects of Endogenous Neurotransmitters on the in vivo Binding of Dopamine and 5-HT Radiotracers in Mice

Rice

2001

Neuropsychopharmacology

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“…Generation of parametric images: A simplified reference tissue model (SRTM) was used to determine binding potential (BP) and ratio of influx (R I ) in a voxel by voxel manner for each subject using a basis function method (Gunn et al, 1997. The cerebellar hemispheres are a suitable reference region as they are devoid of specific 5-HT 1A receptor binding (Pazos et al, 1987;Pike et al, 1996).…”

Section: Definition Of Regionsmentioning

confidence: 99%

Occupancy of Agonist Drugs at the 5-HT1A Receptor

Bantick

Rabiner

Hirani

et al. 2003

Neuropsychopharmacol

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Drugs acting on the 5-HT 1A receptor are used in the treatment of depression, generalized anxiety disorder, and schizophrenia. This study investigated 5-HT 1A receptor occupancy by the 5-HT 1A agonist drugs flesinoxan (a highly selective probe for the 5-HT 1A receptor) and ziprasidone (a novel atypical antipsychotic drug). Using a within-subject design, 14 healthy volunteers each received two positron emission tomography scans using the selective 5-HT 1A antagonist radiotracer [ 11 C]WAY-100635. One scan constituted a baseline, while the other followed either 1 mg flesinoxan or 40 mg ziprasidone orally. In addition, rats were pretreated with intravenous flesinoxan at doses ranging from 0.001 to 5 mg/kg then [ 11 C]WAY-100635 binding measured ex vivo. Cerebral cortical and hippocampal regions of interest, and cerebellar reference regions were sampled to estimate 5-HT 1A receptor occupancy (inferred from reductions in specific radioligand binding). In man, occupancy was not significant despite volunteers experiencing side effects consistent with central serotonergic activity. The mean cerebral cortex occupancy (71 SD) for flesinoxan was 8.7% (713%), and for ziprasidone 4.6% (717%). However, in rats, flesinoxan achieved significant and dose-related occupancy (17-57%) at 0.25 mg/kg and above. We conclude that 5-HT 1A receptor agonists produce detectable occupancy only at higher doses that would produce unacceptable levels of side effects in man, although lower doses are sufficient to produce pharmacological effects. The development of agonist radiotracers may increase the sensitivity of detecting agonist binding, as 5-HT 1A antagonists bind equally to low-and high-affinity receptor states, while agonists bind preferentially to the high-affinity state.

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“…The 5-HT 1A -specific antagonists currently being used for PET investigation of the 5-HT 1A system include [ 11 C]WAY-100635 (Pike et al, 1996), [ 18 F]MPPF (Le Bars et al, 1998), [ 18 F]FCWAY (Carson et al, 2000), and [ 18 F]mefway (Saigal et al, 2006), all of which are structurally related to WAY-100635. In-vitro measurements of B max have been reported with [ 11 C]WAY-100635 and validated by comparison with its tritiated form (Hall et al, 1997), finding high levels of 5-HT 1A receptor expression throughout the frontal, temporal, parietal, and cingulate cortices with the highest receptor density in the hippocampus (including regions CA1, subiculum, and uncus).…”

Section: Introductionmentioning

confidence: 99%

Measurement of 5-HT_1A Receptor Density and in-vivo Binding Parameters of [¹⁸F]mefway in the Nonhuman Primate

Hillmer

Moirano

Ahlers

et al. 2012

J Cereb Blood Flow Metab

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The goal of this work was to characterize the in-vivo behavior of [ 18 F]mefway as a suitable positron emission tomography (PET) radiotracer for the assay of 5-hydroxytryptamine 1A (5-HT 1A ) receptor density (B max ). Six rhesus monkeys were studied using a multiple-injection (M-I) protocol consisting of three sequential bolus injections of [ 18 F]mefway. Injection times and amounts of unlabeled mefway were optimized for the precise measurement of B max and specific binding parameters k off and k on for estimation of apparent K D . The PET time series were acquired for 180 minutes with arterial sampling performed throughout. Compartmental analysis using the arterial input function was performed to obtain estimates for K 1 , k 2 , k off , B max , and K Dapp in the cerebral cortex and raphe nuclei (RN) using a model that accounted for nontracer doses of mefway. Averaged over subjects, highest binding was seen in the mesial temporal and dorsal anterior cingulate cortices with B max values of 42 ± 8 and 36 ± 8 pmol/mL, respectively, and lower values in the superior temporal cortex, RN, and parietal cortex of 24 ± 4, 19 ± 4, and 13 ± 2 pmol/mL, respectively. The K Dapp of mefway for the 5-HT 1A receptor sites was 4.3 ± 1.3 nmol/L. In conclusion, these results show that M-I [ 18 F]mefway PET experiments can be used for the in-vivo measurement of 5-HT 1A receptor density.

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Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11C]WAY-100635

Cited by 206 publications

References 3 publications

Effects of Endogenous Neurotransmitters on the in vivo Binding of Dopamine and 5-HT Radiotracers in Mice

Effects of Endogenous Neurotransmitters on the in vivo Binding of Dopamine and 5-HT Radiotracers in Mice

Occupancy of Agonist Drugs at the 5-HT1A Receptor

Measurement of 5-HT_1A Receptor Density and in-vivo Binding Parameters of [¹⁸F]mefway in the Nonhuman Primate

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Exquisite delineation of 5-HT1A receptors in human brain with PET and [carbonyl-11C]WAY-100635

Cited by 206 publications

References 3 publications

Effects of Endogenous Neurotransmitters on the in vivo Binding of Dopamine and 5-HT Radiotracers in Mice

Effects of Endogenous Neurotransmitters on the in vivo Binding of Dopamine and 5-HT Radiotracers in Mice

Occupancy of Agonist Drugs at the 5-HT1A Receptor

Measurement of 5-HT1A Receptor Density and in-vivo Binding Parameters of [18F]mefway in the Nonhuman Primate

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Measurement of 5-HT_1A Receptor Density and in-vivo Binding Parameters of [¹⁸F]mefway in the Nonhuman Primate