Evaluation of serotonergic transporters using PET and [C-11](+)McN-5652: Assessment of methods

[C-11](+)McN-5652 is an established positron emission tomography tracer use d to assess serotonergic transporter density. Several methods have been use d to analyze [C-11](+)McN-5652 data; however, no evaluation of candidate me thods has been published in detail yet. In this study, compartmental modeli ng using a one-tissue compartment model (K-1, k(2)"), a two-tissue compartm ent model (K-1 to k(4)), and a noncompartmental method that relies on a ref erence region devoid of specific binding sites were assessed. Because of it s low density of serotonergic transporters, white matter was chosen as refe rence. Parameters related to transporter density were the total distributio n volume DV " (= K-1/k(2)", one tissue compartment), DVtot (= K-1/k(1)' (1 + k(3)/k(4)), two tissue compartments), and R-v (= k(3)'/k(4), noncompartme ntal method). The DV ", DVtot, and R-v values extended over a similar range and reflected the known pattern of serotonergic transporters. How ever, al l parameters related to transporter density were markedly confounded by non specific binding. With regard to K-1, the one-tissue compartment model yiel ded markedly lower values, which were, however, more stable. The minimal st udy duration needed to determine stable values for the distribution volume was similar to 60 minutes. The choice of the method to analyze [C-11](+)McN -5652 data depends on the situation. Parametric maps of R-v are useful if n o information on K-1 is needed. If compartmental modeling is chosen, both t he one- and the two-tissue compartment models have advantages. The one-tiss ue compartment model underestimates K-1 but yields more robust values. The distribution volumes calculated with both models contain a similar amount o f information. None of the parameters reflected serotonergic transporter de nsity in a true quantitative manner, as all were confounded by nonspecific binding.