5‐HT radioligands for human brain imaging with PET and SPECT

Paterson, Louise M.; Kornum, Birgitte Rahbek; Nutt, David; Pike, Victor W.; Knudsen, Gitte M.

doi:10.1002/med.20245

Cited by 143 publications

(133 citation statements)

References 409 publications

(716 reference statements)

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…Derivatives of the ligand [ 11 C]NMQ for example could potentially be used for PET in humans (Paterson et al 2011). Also carbon-11 labeled benzoxazole derivatives have been synthesized (Gao et al 2008), but remain to be tested in vivo.…”

Section: -Ht 3 Receptorsmentioning

confidence: 99%

See 1 more Smart Citation

Serotonin and molecular neuroimaging in humans using PET

2011

View full text Add to dashboard Cite

The serotonergic system is one of the most important modulatory neurotransmitter systems in the human brain. It plays a central role in major physiological processes and is implicated in a number of psychiatric disorders. Along with the dopaminergic system, it is also one of the phylogenetically oldest human neurotransmitter systems and one of the most diverse, with 14 different receptors identified up to this day, many of whose function remains to be understood. The system's functioning is even more diverse than the number of its receptors, since each is implicated in a number of different processes. This review aims at illustrating the distribution and summarizing the main functions of the serotonin (5-hydroxytryptamin, 5-HT) receptors as well as the serotonin transporter (SERT, 5-HTT), the vesicular monoamine transporter 2, monoamine oxidase type A and 5-HT synthesis in the human brain. Recent advances in in vivo quantification of these different receptors and enzymes that are part of the serotonergic system using positron emission tomography are described.

show abstract

Section: -Ht 3 Receptorsmentioning

confidence: 99%

“…Nonlabeled ligands for the 5-HT 2C receptor do exist but labeled PET ligands still have low selectivity (Paterson et al 2011) complicating the search for its function in the CNS.…”

Section: -Ht 2b /5-ht 2cmentioning

confidence: 99%

Serotonin and molecular neuroimaging in humans using PET

2011

View full text Add to dashboard Cite

show abstract

“…Second, PET and SPECT suffer from relatively low spatial resolution. Besides these practical limitations, until now studies using 5-HT radioligands have been less successful and are (consequently) less abundant than studies with for example dopaminergic radioligands (Paterson et al, 2011;Saulin et al, 2012;Smith et al, 2002). Thus, there is a clear need for novel, non-invasive methods to assess 5-HT function in humans and especially in psychiatric patients.…”

Section: Introductionmentioning

confidence: 95%

Feasibility of ASL-based phMRI with a single dose of oral citalopram for repeated assessment of serotonin function

Klomp¹,

Caan²,

Denys³

et al. 2012

NeuroImage

View full text Add to dashboard Cite

“…C]WAY100635 has been the most commonly used 5-HT 1A ligand for in vivo Positron Emission Tomography (PET) studies (2). However, being a noncompetitive antagonist at the 5-HT 1A R, it has equal affinity for high agonist (HA) and low agonist (LA) affinity sites of the receptors and therefore cannot detect changes in the ratio of these sites or changes specific to high agonist affinity sites.…”

mentioning

confidence: 99%

Comparison of High and Low Affinity Serotonin 1A Receptors by PET In Vivo in Nonhuman Primates

et al. 2012

View full text Add to dashboard Cite

The serotonin 1A receptor (5-HT 1A R) is implicated in the pathophysiology of a variety of neuropsychiatric and neurodegenerative disorders (1). The antagonist radiotracer [ 11 C]WAY100635 has been the most commonly used 5-HT 1A ligand for in vivo Positron Emission Tomography (PET) studies (2). However, being a noncompetitive antagonist at the 5-HT 1A R, it has equal affinity for high agonist (HA) and low agonist (LA) affinity sites of the receptors and therefore cannot detect changes in the ratio of these sites or changes specific to high agonist affinity sites. In contrast, agonists bind preferentially to the HA state of the receptor, thereby providing a more functionally meaningful measure of the 5-HT 1A R. This hypothesis is supported by the finding that in vitro agonist binding measured by [ . Theoretically, the failure of the system to adjust or maintain the necessary ratio of HA and LA affinity site of receptors may be an important factor in the pathophysiology of several diseases. Obtaining PET scans with both an agonist and antagonist ligand in the same subject enables the quantification of not only the binding to active or Gprotein-coupled receptors (GPCR), but also the ratio of active vs. inactive receptors, which may change without any change in the total binding. Importantly, this ratio determines the number of active receptors or the efficacy of 5-HT transmission by endogenous 5-HT. Moreover, an agonist 5-HT 1A radiotracer is likely to be sensitive to displacement by the endogenous agonist of the receptor and therefore may be useful as a biomarker to measure the changes in the intra-synaptic concentrations of the endogenous 5-HT, to monitor desensitization (down regulation) and sensitization (up regulation) of GPCRs, to provide a better estimate of receptor occupancy for agonist therapeutic agents, and for evaluation of the efficacy of SSRI treatment. However, no in vivo data have been published for a comparison of agonist and antagonist 5-HT 1A tracers as a proof of principle for measurement of high and low affinity states of this receptor. We have recently reported that [11 C]CUMI-101, a 5-HT 1A partial agonist radiotracer (K i = 0.15 nM, E max = 80%), can quantify 5-HT 1A binding with PET in nonhuman primates and human subjects (6 -8 Psychiatry and Behavioral Medicine, Stony Brook University, Stony Brook, NY 11794, USA Received April 22, 2012; Accepted September 7, 2012 Abstract. Serotonin (5-HT) 1A receptors exist in high and low affinity states. Agonist ligands bind preferentially to the high affinity state receptors, providing a more functionally relevant measure than antagonist binding. We now report comparison of 5-HT 1A binding in vivo using both

show abstract

5‐HT radioligands for human brain imaging with PET and SPECT

Cited by 143 publications

References 409 publications

Serotonin and molecular neuroimaging in humans using PET

Serotonin and molecular neuroimaging in humans using PET

Feasibility of ASL-based phMRI with a single dose of oral citalopram for repeated assessment of serotonin function

Comparison of High and Low Affinity Serotonin 1A Receptors by PET In Vivo in Nonhuman Primates

Contact Info

Product

Resources

About