DASB, also known as 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile, is a compound that binds to the serotonin transporter. Labeled with carbon-11 — 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 ...

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 The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special ...

, since it has high selectivity 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'', " ...

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 direction ...

and striatum, 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 pr ...

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 The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cere ...

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 extrace ...

s used in the treatment of major depression 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 Adam; el, Ἀδάμ, Adám; la, Adam is the name given in Genesis 1-5 to the first human. Beyond its use as the name of the first man, ''adam'' is also used in the Bible as a pronoun, individually as "a human" and in a collective sense as " ...

, sup>11C MADAM, sup>11CFM, sup>11CAPA, sup>11C cN5652, and sup>11CNS 4194. A related molecule to DASB, that can be labeled with fluorine-18, 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 ...

there are further radioligands available: sup>123IDAM, sup>123IDAM, sup>123IDAM, and sup>123I

β-CIT RTI(-''4229'')-55, also called RTI-55 or iometopane, is a phenyltropane-based psychostimulant used in scientific research and in some medical applications. This drug was first cited in 1991. RTI-55 is a non-selective dopamine reuptake inhibitor d ...

. A few studies have examined the difference in binding between the radioligands in nonhuman

primate Primates are a diverse order (biology), order of mammals. They are divided into the Strepsirrhini, strepsirrhines, which include the lemurs, galagos, and lorisids, and the Haplorhini, haplorhines, which include the Tarsiiformes, tarsiers and ...

s, as well as in pigs. Other compounds that can be labeled to work as PET radioligands for the study of the serotonin system are, e.g., altanserin and WAY-100635.

Methodological issues

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