JHU/JHMI SAIRP
[11C]DASB is a serotonin (SERT) receptor antagonist. DASB exhibits moderate reversibility, thus Logan analysis is ok but not entirely effective. The cerebellum is considered to be a reference region for serotonin, thus reference tissue methods are applicable.
The methods
Compartmental modeling (blood input)
Rationale: Compartmental modeling with a blood input function is always considered the gold standard method of quantification.
Advantages: The most thorough method, and generally, the most irrefutable technique.
Drawbacks: Arterial blood sampling is required; both the experiment and analysis are relatively difficult. Many groups acquire 120 minute scans - here we usually scan for 90-95 minutes for logistical reasons.
Techniques: First model the cerebellum to estimate non-specific binding. With non-specific binding held fixed, apply modeling to other regions to estimate DASB model parameters. Recommended to hold blood volume fixed. It may also be a good idea to perform a coupled fit with coupling of k4.
Reference tissue modeling
Rationale: There is very little serotonin binding in cerebellum, thus an acceptable reference region exists.
Advantages: Relatively simple method and blood sampling is avoided.
Drawbacks: The kinetics of DASB are somewhat slow, thus reference tissue modeling is prone to bias.
Techniques: Generate TACs, then apply the simplified reference tissue model (SRTM) with cerebellum input. It may help to apply coupled fitting, with coupling of VeR.
Parametric mapping
Rationale: Using a simple analysis method such as Logan graphical analysis or a 1-tissue model fit, parametric mapping is feasible for DASB.
Advantages: Can apply SPM analysis such that the analysis is not dependent upon drawing predefined regions.
Drawbacks: There will be some bias in the voxel-wise estimates.
Techniques: Generate binding potential (BP) maps, normalize to a common template, then perform SPM analysis on the normalized images.