Development of radioligands for imaging of brain norepinephrine transporters in vivo with positron emission tomography.
In the central nervous system (CNS) and in the periphery, specific proteins (transporters) are responsible for the regulation of the synaptic concentrations of the major monoamine neurotransmitters, noradrenaline (NE), serotonin (5-HT) and dopamine (DA). Several reports have shown that the expression of these transporters within the CNS may be altered in patients with certain neurodegenerative or neuropsychiatric disorders. Therefore, in the CNS the monoamine transporters are major targets for existing and developmental drugs. The best known drugs targeting these transporters are the selective 5-HT reuptake inhibitors (SSRIs) (e.g. citalopram, Celexa) that are most frequently used in the treatment of clinical depression. Selective NE reuptake inhibitors (NRIs) have also found use for the treatment of depression and other conditions such as attention deficit hyperactivity (ADHD) disorder. Given that the NE transporter (NET) is also a binding site for cocaine and drugs of abuse, there is a great need for a probe to assess the densities of NET in vivo by brain imaging with either positron emission tomography (PET) or single photon emission tomography (SPET). PET in particular has the potential to measure NET densities quantitatively and with high resolution in the human brain in vivo. The quality of a PET image depends crucially on the radioligand used in the emission measurement. Commonly used radionuclides in PET radioligands are carbon 11 (t(1/2) = 20.4 min) and fluorine-18 (t(1/2) = 109.8 min). This review specifically summarizes the present status of the development of (11)C- or (18)F-labeled ligands as tools for imaging NET in brain with PET in support of neuropsychiatric clinical research and drug development.
Schou
Magnus
M
Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, S-17176 Stockholm, Sweden. magnus.schou@astrazeneca.com
Pike
Victor W
VW
Halldin
Christer
C
D001921:Brain / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000032:analysis* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
D008024:Ligands; D050484:Norepinephrine Plasma Membrane Transport Proteins; D019275:Radiopharmaceuticals