Evaluation of reference tissue model and tissue ratio method for 5-HTT using [123I] ADAM tracer

The serotonin (5-hydroxytryptamine, or 5-HT) transporters (5-HTT) are target-sites for commonly used antidepressants. [^1^2^3I] ADAM is a novel radiotracer that selectively binds the 5-HTT of the central nervous system. The aim for this study was to compare four-parameter model (FPM) with three-parameter model (TPM) from non-invasive reference tissue model (RTM) for 5-HTT quantification using the cerebellum as indirect input function. Furthermore, we compared tracer kinetic model with the tissue ratio (TR) method. The binding potential (BP) values derived from both models were almost the same, but ratio of delivery (R"1) in TPM had smaller standard deviation than the FPM. There was also significant correlation between BP and specific uptake ratio (SUR). In conclusion, simplified reference tissue model (SRTM) was the better choice because of its stability and convenient implementation for non-invasive quantification of brain SPECT studies. The correlation found between BP and SUR supports the use of TR method for quantification of 5-HTT to avoid arterial sampling in dynamic SPECT scan.