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N-Acetyl-N-(2-[18F]fluoroethoxybenzyl)-2-phenoxy-5-pyridinamine .

Authors

Leung K1.

Source

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2008 Aug 12 [updated 2008 Aug 22].

Author information

1
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD, Email: micad@ncbi.nlm.nih.gov

Excerpt

Benzodiazepines are potent psychoactive drugs used for their sedative and anxiolytic properties (1, 2). There are two types of benzodiazepine receptors, which have been designated as central benzodiazepine receptors (CBRs) and peripheral benzodiazepine receptors (PBRs). CBRs are found exclusively in the central nervous system on the membranes of neurons and are coupled to the γ-aminobutyric acid receptor/chloride channel (3). In contrast, PBRs are mitochondrial proteins found in the brain and peripheral tissues (adrenal gland, heart, lung, kidney, and testis) (4); the brain has lower levels of PBR than do the peripheral tissues, and both glial cells and macrophages contain high levels of PBR (5-7). Increased PBR expression after brain injury or neuroinflammation is associated with microglial activation, such as occurs with the neuronal damage that accompanies several neurodegenerative diseases, including Alzheimer’s disease, Wernicke’s encephalopathy, multiple sclerosis, and epilepsy. PBRs have been studied in vivo with positron emission tomography (PET) using 1-(2-chlorophenyl)-N-[11C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ([11C]PK11195), an isoquinoline carboxamide with specific PBR antagonistic activity. [11C]PK11195 has been developed as a PET agent for non-invasive studies of microglia and macrophage activation in the brain, lung, and heart [PuBMed]. However, accumulation of this tracer in the brain is limited. N-(2,5-Dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide (DAA1106) is a selective agonist used to study PBRs in the central nervous system (8, 9). DAA1106 was reported to have a higher affinity for PBRs in mitochondrial fractions of rat and monkey brains than PK11195 (8, 9). Therefore, both tracers are able to cross the normal cell membrane to reach the mitochondrial receptor sites. N-(5-Fluoro-2-phenoxyphenyl)-N-(2-[18F]fluoroethyl-5-methoxybenzyl)acetamide ([18F]FEDAA1106) and 11C-labeled DAA1106 ([11C]DAA1106) have been developed as potential PET ligands with highly selective and specific binding to PBR. N-Acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine (PBR28), which has an aryloxyanilide structure, has been shown to have high affinity and selectivity for PBR (10). N-Acetyl-N-(2-[11C]methoxybenzyl)-2-phenoxy-5-pyridinamine ([11C]PBR28) has been developed for imaging PBR in the brain (11). N-Acetyl-N-(2-[18F]fluoroethoxybenzyl)-2-phenoxy-5-pyridinamine ([18F]FEPPA), an analog of [11C]PBR28, is being evaluated as a PET imaging agent for PBR in the brain (12).

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