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Quantification of ¹¹C-MADAM Binding to the Serotonin Transporter in the Human Brain

¹ Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden
² Department of Sensory and Integrative Medicine, Division of Functional Imaging, Niigata University Graduate School of Medicine and Dental Sciences, Asahimachi-dori Niigata, Japan

View larger version (11K): [in a new window]   FIGURE 1. The 3- and 4-compartment model. The 4 compartments correspond to the radioactivity concentration of unchanged radioligand in plasma (CP), unbound radioligand in brain (CF), nonspecifically bound radioligand in brain (CNS), and radioligand specifically bound to receptors (CB). With the assumption that CF and CNS rapidly coalesce, they can be substituted with one compartment representing nondisplaceable radioligand (CN, dotted line) (A). In the 2-compartment model, CB and CN are substituted by one tissue compartment (CT) (B).

View larger version (97K): [in a new window]   FIGURE 2. Summation image based on data from frames 6–20 showing regional radioactivity after intravenous injection of 11C-MADAM. Projections are, clockwise from top left, sagittal (A), transaxial (B), and coronal (C).

View larger version (28K): [in a new window]   FIGURE 3. Time–activity curves of ROIs and of plasma input function in one subject.

View larger version (17K): [in a new window]   FIGURE 4. (A) Labeled metabolites detected by HPLC (1 and 2) were more polar than the mother compound 11C-MADAM (3) (based on 4-min sample from one subject). (B) Fraction of detected radioactivity in plasma: 1, 2 and 3 correspond to the 3 peaks in HPLC (mean ± SD, n = 9).

View larger version (17K): [in a new window]   FIGURE 5. Experimental values of regional activity and corresponding fitted curves as obtained by the 2CM, the unconstrained 3CM (3CM(1)), and the 3CM with the K1/k2 ratio given by that of cerebellum (3CM(2)).

View larger version (18K): [in a new window]   FIGURE 6. Linear graphic analyses of 11C-MADAM binding in hippocampal complex and frontal cortex (A) and cerebellum (B). Slope of linear phase corresponds to the DV.

View larger version (21K): [in a new window]   FIGURE 7. Experimental values for regional radioactivity in putamen and cerebellum presented together with calculated values of total radioactivity in putamen, specific binding, and free fraction according to 3CM(1) (A) and 3CM(2) (B).