PT - JOURNAL ARTICLE AU - Ramin V. Parsey AU - Ashish Ojha AU - R. Todd Ogden AU - Kjell Erlandsson AU - Dileep Kumar AU - Marguerite Landgrebe AU - Ronald Van Heertum AU - J. John Mann TI - Metabolite Considerations in the In Vivo Quantification of Serotonin Transporters Using <sup>11</sup>C-DASB and PET in Humans DP - 2006 Nov 01 TA - Journal of Nuclear Medicine PG - 1796--1802 VI - 47 IP - 11 4099 - http://jnm.snmjournals.org/content/47/11/1796.short 4100 - http://jnm.snmjournals.org/content/47/11/1796.full SO - J Nucl Med2006 Nov 01; 47 AB - PET studies of the serotonin (5-hydroxytryptamine, or 5-HT) transporter are increasingly using 11C-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile (DASB). We noted that the percentage of unmetabolized 11C-DASB is often lower at 2 min after injection than at 12 min. We hypothesized that this is due to initial “trapping” of the unmetabolized 11C-DASB compound in the lung, a major 5-HT transporter site and dose-limiting organ. To determine whether binding to an extracranial pool of 5-HT transporters contributes to the lower initial level of unmetabolized 11C-DASB, we examined the effects of sertraline. Methods: Eleven healthy volunteers had 2 11C-DASB PET scans on the same day, and 6 of the 11 had a third scan after sertraline administration. The unmetabolized 11C-DASB fraction was measured in arterial plasma as a function of time and was fit with 2 exponentials with no damping, power function damping, or no damping with the first point removed. Results: Power function damping best fit the data as assessed by visual inspection and residuals and resulted in greater distribution volumes than did no damping with the first point removed. Test–retest reproducibility improved when power function damping was used, as compared with no damping with the first point removed. Oral sertraline raised the 2-min unmetabolized 11C-DASB percentage. Conclusion: Measurement and fitting of early metabolism time points improves curve fitting, significantly affects volume-of-distribution determination, and improves test–retest reproducibility. Saturation of lung 5-HT transporters by sertraline prevents the initial trapping of 11C-DASB. Initial trapping of high-affinity radioligands may be important in the quantification of the binding of other ligands with a high concentration of binding sites in the lungs.