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Small Animal Imaging Resource Program @ Johns Hopkins

JHU/JHMI SAIRP

[11C]DASB

[11C]DASB is a serotonin (SERT) receptor antagonist. DASB exhibits moderate reversibility, and most tissue regions can be quantified reliably in a 90 minute dynamic study. The cerebellum is often used as a reference region for SERT, and is used when applying reference tissue methods for quantification of DASB studies.

Studies of significance
First in man: Houle et al, 2000
Test-retest: Frankle et al, 2005, Kim et al, 2006

Methods of Quantification

Quantification

Compartmental modeling (blood input)
For compartmental modeling with a blood input function, a 1-tissue model is preferred to a 2-tissue model for [11C]DASB time-activity curves Ginovart et al, 2001

Blood metabolism
An interesting feature of [11C]DASB pharmacokinetics is the plasma metabolite profile. For nearly all tracers the plasma metabolite fraction increases continuously as expected. However, for [11C]DASB the fraction increases for 3-5 minutes, then decreases, then increases again. The mechanism for this effect is likely the binding of [11C]DASB to SERT in lung. Following a bolus injection, [11C]DASB occupies lung SERT which is protected from metabolism. As [11C]DASB is released from lung SERT, the plasma metabolite fraction decreases temporarily before increasing again Parsey et al, 2006.

Reference tissue modeling
There is very little SERT binding in cerebellum, thus the cerebellum is considered to be an acceptable reference region for quantification of [11C]DASB specific binding. The multilinear method of Ichise Ichise et al, 2005 has been shown to give reliable and reproducible results for quantifiction of [11C]DASB binding.

Parameter coupling
Parameter coupling refers to the fitting of multiple regions simultaneously with coupling of common parameters. The motivation for parameter coupling is to reduce the total number of fitted parameters. By fitting fewer parameters with the same amount of data, the precision of parameter estimation should be improved. For [11C]DASB, parameter coupling of the simplified reference tissue model has been shown to improve the agreement with binding potential estimates obtained with a blood input model, and the improvement is especially notable in low binding regions.

DASB

Target: Serotonin transporter (SERT)

LogP: 3.03

Molecular Weight: 283

Affinity for SERT: 0.54 nM

Protein binding: 89%

Radiosynthesis: synthesis methylation

Chemical name: [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile