DASB, also known as 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, is a compound that binds to the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein t ...

. Labeled with

carbon-11 Carbon (6C) has 15 known isotopes, from to , of which and are stable. The longest-lived radioisotope is , with a half-life of years. This is also the only carbon radioisotope found in nature—trace quantities are formed cosmogenically by t ...

— a radioactive isotope — it has been used as a

radioligand A radioligand is a radioactive biochemical substance (in particular, a ligand that is radiolabeled) that is used for diagnosis or for research-oriented study of the receptor systems of the body. In a neuroimaging application the radioligand is i ...

neuroimaging Neuroimaging is the use of quantitative (computational) techniques to study the structure and function of the central nervous system, developed as an objective way of scientifically studying the healthy human brain in a non-invasive manner. Incr ...

with

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

(PET) since around year 2000. In this context it is regarded as one of the superior radioligands for PET study of the serotonin transporter in the brain, since it has high

selectivity Selectivity may refer to: Psychology and behaviour * Choice, making a selection among options * Discrimination, the ability to recognize differences * Socioemotional selectivity theory, in social psychology Engineering * Selectivity (radio), a ...

for the serotonin transporter. The DASB image from a human PET scan shows high binding in the

midbrain The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', "m ...

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directio ...

and

striatum The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives glutamate ...

, moderate binding in the

medial temporal lobe The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe is involved in pro ...

and anterior cingulate, and low binding in

neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, ...

. The cerebellum is often regarded as a region with no specific serotonin transporter binding and the brain region is used as a reference in some studies. Since the serotonin transporter is the target of

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...

s used in the treatment of

major depression Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introd ...

it has been natural to examine DASB binding in depressed patients. Several such research studies have been performed. There are a number of alternative PET radioligands for imaging the serotonin transporter: sup>11C ADAM, sup>11C

MADAM Madam (), or madame ( or ), is a polite and formal form of address for women in the English language, often contracted to ma'am (pronounced in American English and this way but also in British English). The term derives from the French ''mad ...

, sup>11CFM, sup>11CAPA, sup>11C cN5652, and sup>11CNS 4194. A related molecule to DASB, that can be labeled with

fluorine-18 Fluorine-18 (18F) is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380(6) u and its half-life is 109.771(20) minutes. It decays by positron emission 96% of the time and electron capture 4% of the time. ...

, has also been suggested as a PET radioligand. With

single-photon emission computed tomography Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...

(SPECT) using the radioisotope

iodine-123 Iodine-123 (123I) is a radioactive isotope of iodine used in nuclear medicine imaging, including single-photon emission computed tomography (SPECT) or SPECT/CT exams. The isotope's half-life is 13.2230 hours; the decay by electron capture to tellu ...

there are further radioligands available: sup>123IDAM, sup>123IDAM, sup>123IDAM, and sup>123I β-CIT. A few studies have examined the difference in binding between the radioligands in nonhuman

primate Primates are a diverse order of mammals. They are divided into the strepsirrhines, which include the lemurs, galagos, and lorisids, and the haplorhines, which include the tarsiers and the simians (monkeys and apes, the latter including human ...

s, as well as in

pig The pig (''Sus domesticus''), often called swine, hog, or domestic pig when distinguishing from other members of the genus '' Sus'', is an omnivorous, domesticated, even-toed, hoofed mammal. It is variously considered a subspecies of ''Sus s ...

s. Other compounds that can be labeled to work as PET radioligands for the study of the serotonin system are, e.g.,

altanserin Altanserin is a compound that binds to the 5-HT2A receptor (5-Hydroxytryptamine (serotonin) 2A receptor). Labeled with the isotope fluorine-18 it is used as a radioligand in positron emission tomography (PET) studies of the brain, i.e., studies ...

and

WAY-100635 WAY-100635 is a piperazine drug and research chemical widely used in scientific studies. It was originally believed to act as a selective 5-HT1A receptor antagonist, but subsequent research showed that it also acts as potent full agonist at t ...

Methodological issues

The

binding potential In pharmacokinetics and receptor-ligand kinetics the binding potential (BP) is a combined measure of the density of "available" neuroreceptors and the affinity of a drug to that neuroreceptor. Description Consider a ligand receptor binding syst ...

of DASB can be estimated with kinetic modeling on a series of brain scans. A test-retest

reproducibility Reproducibility, also known as replicability and repeatability, is a major principle underpinning the scientific method. For the findings of a study to be reproducible means that results obtained by an experiment or an observational study or in ...

PET study indicates that sup>11CASB can be used to measure the serotonin transporter parameters with high reliability in receptor-rich brain regions. When the DASB neuroimages are analyzed the kinetic models suggested by Ichise and coworkers can be employed to estimate the

. A test-retest

experiment has been performed to evaluate this approach.

Studies

Besides the studies listed below a few occupancy studies have been reported.

References

{{Serotonergics Treatment of bipolar disorder Nitriles Thioethers PET radiotracers