Brain serotonergic circuitries

Brain serotonergic circuitries interact with other neurotransmitter systems on a multitude of different molecular levels. In humans, as in other mammalian species, serotonin (5-HT) plays a modulatory role in almost every physiological function. Furthermore, serotonergic dysfunction is thought to be implicated in several psychiatric and neurodegenerative disorders. We describe the neuroanatomy and neurochemistry of brain serotonergic circuitries. The contribution of emergent in vivo imaging methods to the regional localization of binding site receptors and certain aspects of their functional connectivity in correlation to behavior is also discussed. 5-HT cell bodies, mainly localized in the raphe nuclei, send axons to almost every brain region. It is argued that the specificity of the local chemocommunication between 5-HT and other neuronal elements mainly depends on mechanisms regulating the extracellular concentration of 5-HT the diversity of high-affinity membrane receptors, and their specific transduction modalities.

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Discovery and labeling of a homochiral high affinity 3,4-diarylpyrazoline as a candidate radioligand for in vivo imaging of cannabinoid type-1 receptors

NeuroImage ◽

10.1016/j.neuroimage.2008.04.059 ◽

2008 ◽

Vol 41 ◽

pp. T90 ◽

Cited By ~ 1

Author(s):

Sean R. Donohue ◽

S.J. Finnema ◽

P. Truong ◽

J. Andersson ◽

B. Gulyás ◽

...

Keyword(s):

In Vivo Imaging ◽

High Affinity

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Design, synthesis, biochemical evaluation, radiolabeling and in vivo imaging with high affinity class-IIa histone deacetylase inhibitor for molecular imaging and targeted therapy

European Journal of Medicinal Chemistry ◽

10.1016/j.ejmech.2021.114011 ◽

2021 ◽

pp. 114011

Author(s):

Nashaat Turkman ◽

Daxing Liu ◽

Isabella Pirola

Keyword(s):

Targeted Therapy ◽

Molecular Imaging ◽

Histone Deacetylase ◽

In Vivo Imaging ◽

Histone Deacetylase Inhibitor ◽

Design Synthesis ◽

High Affinity ◽

Deacetylase Inhibitor ◽

Biochemical Evaluation

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Novel Peptide Sequence (“IQ-tag”) with High Affinity for NIR Fluorochromes Allows Protein and Cell Specific Labeling for In Vivo Imaging

PLoS ONE ◽

10.1371/journal.pone.0000665 ◽

2007 ◽

Vol 2 (7) ◽

pp. e665 ◽

Cited By ~ 13

Author(s):

Kimberly A. Kelly ◽

Jonathan Carson ◽

Jason R. McCarthy ◽

Ralph Weissleder

Keyword(s):

In Vivo Imaging ◽

Peptide Sequence ◽

High Affinity

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Discovery and Labeling of High-Affinity 3,4-Diarylpyrazolines as Candidate Radioligands for In Vivo Imaging of Cannabinoid Subtype-1 (CB1) Receptors

Journal of Medicinal Chemistry ◽

10.1021/jm800329z ◽

2008 ◽

Vol 51 (18) ◽

pp. 5608-5616 ◽

Cited By ~ 16

Author(s):

Sean R. Donohue ◽

Victor W. Pike ◽

Sjoerd J. Finnema ◽

Phong Truong ◽

Jan Andersson ◽

...

Keyword(s):

In Vivo Imaging ◽

Cb1 Receptors ◽

High Affinity

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High-affinity Near-infrared Fluorescent Small-molecule Contrast Agents for In Vivo Imaging of Prostate-specific Membrane Antigen

Molecular Imaging ◽

10.2310/7290.2005.05163 ◽

2005 ◽

Vol 4 (4) ◽

pp. 7290.2005.05163 ◽

Cited By ~ 53

Author(s):

Valerie Humblet ◽

Rena Lapidus ◽

Larry R. Williams ◽

Takashi Tsukamoto ◽

Camilo Rojas ◽

...

Keyword(s):

Prostate Cancer ◽

Small Molecule ◽

In Vivo Imaging ◽

Near Infrared ◽

Expression System ◽

High Yield ◽

Definitive Treatment ◽

Fluorescent Light ◽

High Affinity

Surgical resection remains a definitive treatment for prostate cancer. Yet, prostate cancer surgery is performed without image guidance for tumor margin, extension beyond the capsule and lymph node positivity, and without verification of other occult metastases in the surgical field. Recently, several imaging systems have been described that exploit near-infrared (NIR) fluorescent light for sensitive, real-time detection of disease pathology intraoperatively. In this study, we describe a high-affinity (9 nM), single nucleophile-containing, small molecule specific for the active site of the enzyme PSMA. We demonstrate production of a tetra-sulfonated heptamethine indocyanine NIR fluorescent derivative of this molecule using a high-yield LC/MS purification strategy. Interestingly, NIR fluorophore conjugation improves affinity over 20-fold, and we provide mechanistic insight into this observation. We describe the preparative production of enzymatically active PSMA using a baculovirus expression system and an adenovirus that co-expresses PSMA and GFP. We demonstrate sensitive and specific in vitro imaging of endogenous and ectopically expressed PSMA in human cells and in vivo imaging of xenograft tumors. We also discuss chemical strategies for improving performance even further. Taken together, this study describes nearly complete preclinical development of an optically based small-molecule contrast agent for image-guided surgery.

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