DASB


DASB, also known as 3-amino-4--benzonitrile, is a compound that binds to the serotonin transporter.
Labeled with carbon-11 — a radioactive isotope — it has been used as a radioligand in neuroimaging with positron emission tomography 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 for the serotonin transporter.
The DASB image from a human PET scan shows high binding in the midbrain, thalamus and striatum, moderate binding in the medial temporal lobe and anterior cingulate, and low binding in neocortex.
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 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: ADAM, MADAM, AFM, DAPA, McN5652, and -NS 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 using the radioisotope iodine-123 there are further radioligands available: ODAM, IDAM, ADAM, and β-CIT.
A few studies have examined the difference in binding between the radioligands in nonhuman primates,
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 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.
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.
WhatResultSubjectsRef.
5-HTTLPR LALA serotonin transporter genotypeIncrease in putamen43/30
5-HTTLPR LALA serotonin transporter genotypeIncrease in midbrain19
5-HTTLPR LALA serotonin transporter genotypeNo difference63
AgeNo effect found
Body mass indexInverse correlation ?
SeasonalityHigher in winter in putamen and caudate54
SeasonalityHigher in fall and winter88
NEO PI-R NeuroticismPositive correlation in thalamus31 males
Disease---
Depressed during major depressive episodesNo difference found20+20
Depressed with highly negativistic "dysfunctional attitudes" during major depressive episodesIncrease in prefrontal cortex, anterior cingulate, thalamus, bilateral caudate, and bilateral putamen20+20
Recovered depressed patientsNo difference found24+20 males
Unipolar depressionIncrease in thalamus, insula and striatum18+34
Unmedicated unipolar major depressionReduced 5-HTT availability in the thalamus
TCI anxiety in unmedicated unipolar major depressionReduced 5-HTT availability in the thalamus, midbrain and amygdala
Bipolar depressionIncrease in thalamus, insula and striatum18+34
Bipolar depressionDecrease in midbrain, amygdala, hippocampus, thalamus, putamen, and anterior cingulate cortex18+41
Obsessive compulsive disorderReduction and correlation with severity in thalamus and midbrain9+19
AlcoholismNo significant alteration30 + 18
Parkinson's diseaseReduction in forebrain5+8
Non-depressed Parkinson's diseaseDecreased binding in caudate, midbrain, putamen, orbitofrontal cortex and dorsolateral prefrontal cortex
Depressed Parkinson's disease patientsIncrease in prefrontal and dorsolateral cortices7+7
Drug/intervention---
Abstinent MDMA usersGlobal reduction23+19
Former MDMA users and polydrug usersNo significant difference in brain regions examined12+9+19
Reduced synaptic serotonin 8
Lowering of brain serotonin No change observed25