DASB is a compound that binds to the serotonin transporter

Serotonin transporter

The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...

.
Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand

Radioligand

A radioligand is a radioactive biochemical substance that is used for diagnosis or for research-oriented study of the receptor systems of the body....

 in neuroimaging

Neuroimaging

Neuroimaging includes the use of various techniques to either directly or indirectly image the structure, function/pharmacology of the brain...

 with positron emission tomography

Positron emission tomography

Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

 (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

Brain

The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...

,
since it has high selectivity

Selectivity

Selectivity may refer to:* Selectivity , in radio transmission* Binding selectivity, in pharmacology* Functional selectivity, in pharmacology* Socioemotional selectivity theory, in social psychology...

 for the serotonin transporter.

The DASB image from a human PET scan shows high binding in the midbrain, thalamus

Thalamus

The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...

 and striatum

Striatum

The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...

, moderate binding in the medial temporal lobe and anterior cingulate, and low binding in neocortex

Neocortex

The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...

.
The cerebellum

Cerebellum

The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...

 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 SSRIs 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: [¹¹C]ADAM, [¹¹C]AFM, [¹¹C]DAPA, [¹¹C]McN5652

McN5652

McN5652 is a molecule that can be radiolabeled and then used as a radioligand in positron emission tomography studies. The [11C]--McN5652 enantiomer binds to the serotonin transporter....

, and [¹¹C]-NS 4194.
A related molecule to DASB, that can be labeled with fluorine-18

Fluorine-18

Fluorine-18 is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380 u and its half-life is 109.771 minutes....

, has also been suggested as a PET radioligand.
With single-photon emission computed tomography (SPECT) using the radioisotope iodine-123

Iodine-123

Iodine-123 is a radioactive isotope of iodine used in nuclear medicine imaging, including single photon emission computed tomography . The isotope's half-life is 13.22 hours; the decay by electron capture to tellurium-123 emits gamma radiation with predominant energies of 159 keV and 127 keV...

 there are further radioligands available: [¹²³I]ODAM, [¹²³I]IDAM, [¹²³I]ADAM, and [¹²³I]β-CIT.
A few studies have examined the difference in binding between the radioligands in nonhuman primate

Primate

A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...

s,
as well as in pig

Pig

A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...

s.

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

Altanserin

Altanserin is a compound that binds to the 5-HT2A receptor .It is a yellowish solid.Labeled with the isotope fluorine-18 it is used as a radioligand in positron emission tomography studies of the brain, i.e., studies of the serotonin-2A neuroreceptors.Besides human neuroimaging studies altanserin...

 and WAY-100635

WAY-100635

WAY-100,635 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 the D4 receptor. It is sometimes referred to as a silent...

.

Methodological issues

The binding potential

Binding potential

In pharmacokinetics and receptor-ligand kinetics the binding potential 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 system...

 of DASB can be estimated with kinetic modeling on a series of brain scans.

A test-retest

Test-retest

Test-restest may refer to:*Test-retest reliability*Monitoring by performing frequent tests...

 reproducibility

Reproducibility

Reproducibility is the ability of an experiment or study to be accurately reproduced, or replicated, by someone else working independently...

 PET study indicates that [¹¹C]DASB 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

Binding potential

In pharmacokinetics and receptor-ligand kinetics the binding potential 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 system...

.
A test-retest

Test-retest

Test-restest may refer to:*Test-retest reliability*Monitoring by performing frequent tests...

 reproducibility

Reproducibility

Reproducibility is the ability of an experiment or study to be accurately reproduced, or replicated, by someone else working independently...

 experiment has been performed to evaluate this approach.

Studies

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

DASB binding neuroimaging studies (patients compared to healthy control subjects).

What	Result	Subjects	Ref.
5-HTTLPR 5-HTTLPR 5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...  LALA serotonin transporter genotype	Increase in putamen Putamen The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...	43/30
5-HTTLPR 5-HTTLPR 5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...  LALA serotonin transporter genotype	Increase in midbrain	19
5-HTTLPR 5-HTTLPR 5-HTTLPR is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter.Since the polymorphism was identified in the middle of the 1990s,...  LALA serotonin transporter genotype	No difference	63
Age	No effect found
Body mass index Body mass index The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...	Inverse correlation (?)	?
Seasonality Seasonality In statistics, many time series exhibit cyclic variation known as seasonality, periodic variation, or periodic fluctuations. This variation can be either regular or semi regular....	Higher in winter in putamen Putamen The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...  and caudate Caudate Caudate can refer to:* Caudate nucleus* Caudate lobe of liver* Cauda equina* Members of the Caudata order....	54
Seasonality Seasonality In statistics, many time series exhibit cyclic variation known as seasonality, periodic variation, or periodic fluctuations. This variation can be either regular or semi regular....	Higher in fall and winter	88
NEO PI-R Neuroticism Neuroticism Neuroticism is a fundamental personality trait in the study of psychology. It is an enduring tendency to experience negative emotional states. Individuals who score high on neuroticism are more likely than the average to experience such feelings as anxiety, anger, guilt, and depressed mood...	Positive correlation in thalamus Thalamus The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...	31 males
Disease
Depressed during major depressive episode Major depressive episode A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday... s	No difference found	20+20
Depressed with highly negativistic "dysfunctional attitudes" during major depressive episode Major depressive episode A major depressive episode is the cluster of symptoms of major depressive disorder. The description has been formalised in psychiatric diagnostic criteria such as the DSM-IV and ICD-10, and is characterized by severe, highly persistent depression, and a loss of interest or pleasure in everyday... s	Increase in prefrontal cortex Prefrontal cortex The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior... , anterior cingulate, thalamus Thalamus The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections... , bilateral caudate Caudate Caudate can refer to:* Caudate nucleus* Caudate lobe of liver* Cauda equina* Members of the Caudata order.... , and bilateral putamen Putamen The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...	20(?)+20
Recovered depressed Clinical depression Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...  patients	No difference found	24+20 males
Unipolar depression	Increase in thalamus Thalamus The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections... , insula Insular cortex In each hemisphere of the mammalian brain the insular cortex is a portion of the cerebral cortex folded deep within the lateral sulcus between the temporal lobe and the frontal lobe. The cortical area overlying it towards the lateral surface of the brain is the operculum...  and striatum Striatum The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...	18+34
Unmedicated unipolar major depression	Reduced 5-HTT availability in the thalamus Thalamus The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
TCI Temperament and Character Inventory Temperament and Character Inventory is an inventory for personality traits devised by Cloninger et al.It is closely related to and an outgrowth of Tridimensional Personality Questionnaire ,...  anxiety Anxiety Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...  in unmedicated unipolar major depression	Reduced 5-HTT availability in the thalamus Thalamus The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections... , midbrain and amygdala Amygdala The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
Bipolar depression	Increase in thalamus Thalamus The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections... , insula Insular cortex In each hemisphere of the mammalian brain the insular cortex is a portion of the cerebral cortex folded deep within the lateral sulcus between the temporal lobe and the frontal lobe. The cortical area overlying it towards the lateral surface of the brain is the operculum...  and striatum Striatum The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...	18+34
Bipolar depression	Decrease in midbrain, amygdala Amygdala The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-... , hippocampus Hippocampus The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in... , thalamus Thalamus The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections... , putamen Putamen The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus... , and anterior cingulate cortex Anterior cingulate cortex The anterior cingulate cortex is the frontal part of the cingulate cortex, that resembles a "collar" form around the corpus callosum, the fibrous bundle that relays neural signals between the right and left cerebral hemispheres of the brain...	18+41
Obsessive compulsive disorder	Reduction and correlation with severity in thalamus Thalamus The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...  and midbrain	9+19
Alcoholism Alcoholism Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...	No significant alteration	30 + 18
Parkinson's disease Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system...	Reduction in forebrain	5+8
Non-depressed Parkinson's disease Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system...	Decreased binding in caudate, midbrain, putamen, orbitofrontal cortex and (non-significantly) dorsolateral prefrontal cortex
Depressed Parkinson's disease Parkinson's disease Parkinson's disease is a degenerative disorder of the central nervous system...  patients	Increase in prefrontal Prefrontal cortex The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...  and dorsolateral cortices	7+7
Drug/intervention
Abstinent MDMA ('Ecstasy') users	Global reduction	23+19
Former MDMA users and polydrug users	No significant difference in brain regions examined	12+9+19
Reduced synaptic serotonin Serotonin Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...  (by rapid tryptophan Tryptophan Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...  depletion)	(small reduction in binding potential)	8
Lowering of brain serotonin (by acute tryptophan Tryptophan Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG... depletion)	No change observed	25 (14)