Titre du document / Document title

PET imaging of norepinephrine transporters

Titre de regroupement

PET and SPECT in drug evaluation and drug design: Novel techniques

Auteur(s) / Author(s)

DING Yu-Shin ⁽¹⁾ ; LIN Kuo-Shyan ⁽¹⁾ ; LOGAN Jean ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Chemistry and Medical Departments, Brookhaven National Laboratory, Upton, New York 11973, ETATS-UNIS

Résumé / Abstract

The involvement of the norepinephrine transporter (NET) in the pathophysiology and treatment of attention deficit hyperactivity disorder (ADHD), substance abuse, neurodegenerative disorders (e.g., Alzheimer's disease (AD) and Parkinson's disease (PD)) and depression has long been recognized. However, many of these important findings have resulted from studies in vitro using postmortem tissues; as of now, these results have never been verified via in vivo methods because brain imaging of NET in living systems has been hampered due to the lack of suitable radioligands. The fact that all three monoamine (dopamine, norepinephrine, and serotonin) transporters (DAT, NET and SERT) are involved in various neurological and psychiatric diseases further emphasizes the need to develop suitable NET ligands so that researchers will be able to probe the contributions of each monoamine transporter system to specific CNS disorders. In this review article, the design and biological evaluation of several radioligands for imaging the brain NET system with PET are discussed. Based on these characterization studies, including C-11 labeled desipramine (DMI), 2-hydroxydesipramine (HDMI), talopram, talsupram, nisoxetine (Nis), oxaprotiline (Oxap), lortalamine (Lort) and C-11 and F-18 derivatives of reboxetine (RB), methylreboxetine (MRB) and their individual (R, R) and (S, S) enantiomers, in conjunction with studies with radiolabeled 4-iodo-tomoxetine and 2-iodo-nisoxetine, we have identified the superiority of (S, S)-[¹¹C]MRB and the suitability of the MRB analogs as potential NET ligands for PET. In contrast, Nis, Oxap and Lort displayed high uptake in striatum (higher than thalamus). The use of these ligands is further limited by high non-specific binding and relatively low specific signal, as is characteristic of many earlier NET ligands. Thus, to our knowledge, (S, S)-[¹¹C]MRB remains by far the most promising NET ligand for PET studies.

Revue / Journal Title

Current pharmaceutical design   ISSN 1381-6128 

Source / Source

2006, vol. 12, n^o30, pp. 3831-3845 [15 page(s) (article)] (118 ref.)

Langue / Language

Anglais

Editeur / Publisher

Bentham, Sharjah, EMIRATS ARABES UNIS  (1995) (Revue)

Mots-clés anglais / English Keywords

Central nervous system ; Neurotransmitter ; Catecholamine ; Reuptake inhibitor ; Mood disorder ; Radionuclide study ; Antidepressant agent ; Psychotropic ; Norepinephrine ; Membrane transport ; Carrier protein ; Ligand binding ; Review ; Nisoxetine ; Reboxetine ; Drug addiction ; Central nervous system disease ; Degenerative disease ; In vivo ; Encephalon ; Radiolabelling ; Emission tomography ; Scintigraphic agent ; Positron emission tomography ;

Mots-clés français / French Keywords

Système nerveux central ; Neurotransmetteur ; Catécholamine ; Inhibiteur recapture ; Trouble humeur ; Exploration radioisotopique ; Transporteur de la noradrénaline ; Antidépresseur ; Psychotrope ; Noradrénaline ; Transport membranaire ; Protéine transport ; Fixation ligand ; Article synthèse ; Nisoxétine ; Réboxétine ; Toxicomanie ; Système nerveux central pathologie ; Maladie dégénérative ; In vivo ; Encéphale ; Marquage radioisotopique ; Tomoscintigraphie ; Agent scintigraphique ; Tomographie émission positon ;

Mots-clés espagnols / Spanish Keywords

Sistema nervioso central ; Neurotransmisor ; Catecolamina ; Inhibidor recaptura ; Trastorno humor ; Exploración radioisotópica ; Antidepresor ; Psicotropo ; Noradrenalina ; Transporte membranal ; Proteína transportador ; Fijación ligando ; Artículo síntesis ; Nisoxetina ; Reboxetina ; Toxicomanía ; Sistema nervosio central patología ; Enfermedad degenerativa ; In vivo ; Encéfalo ; Marcación radioisotópica ; Tomocentelleografía ; Agente centelleográfico ; Tomografía emisión positrones ;

Mots-clés d'auteur / Author Keywords

Norepinephrine transporter ; PET ; depression ; substance abuse ; ADHD ; methylreboxetine ; reboxetine ; nisoxetine ;

Localisation / Location

INIST-CNRS, Cote INIST : 26320, 35400014305123.0010