The SPECT tracer [123I]ADAM binds selectively to serotonin transporters: a double-blind, placebo-controlled study in healthy young men

Purpose  

The tracer ¹²³I-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine ([¹²³I]ADAM) has been developed to image serotonin transporters (SERTs) with SPECT. Preclinical studies have shown that [¹²³I]ADAM binds selectively to SERTs. Moreover, initial human studies have shown that [¹²³I]ADAM binding could be blocked by selective serotonin reuptake inhibitors (SSRIs). However, in humans it has not been proven that [¹²³I]ADAM binds selectively to SERTs.     

Phase 1 clinical study of 123I-FP-CIT, a new radioligand for evaluating dopamine transporter by SPECT (II): Tracer kinetics in the brain

The kinetics of 123I-FP-CIT in the brain for healthy subjects were studied. Twelve dynamic SPECT data sets (0- to 6-hr after an intravenous injection) from a Phase 1 clinical trial of 123I-FP-CIT were analyzed. Tracer concentrations in the striatum, midbrain, cerebellum and cerebral cortex were measured on the SPECT images co-registered with the corresponding MR images. High tracer accumulation was observed in the striatum, which peaked at 60 min post-injection, followed by slow elimination (3%/hr). The kinetics were similar both in the cerebellum and in the cerebral cortex, which peaked at 15 min post-injection, followed by rapid elimination. Tracer accumulation in the midbrain was higher than in the cerebellum and cerebral cortex. The striatal specific/nonspecific binding ratio ((striatal-occipital)/occipital concentration ratio) was stable at 3-hr post-injection and later at a value of 3, suggesting that the specific binding of 123I-FP-CIT could be evaluated from a single SPECT image at 3- to 6-hr post-injection. The specific/nonspecific binding ratio at 4-hr post-injection showed a negative correlation with aging (r = -0.70, p = 0.01), with a decrease rate of 11%/decade (95% confidence interval: 3%-19%/decade).     

123I-ADAM binding to serotonin transporters in patients with major depression and healthy controls: a preliminary study.

The serotonergic system may play an important role in the pathophysiology of major depressive disorder (MDD). Few imaging studies have examined serotonin transporter (SERT) binding in patients with MDD. We hypothesized that SERT binding activity may be altered in patients with MDD. This study compared SERT binding in patients with MDD with that in healthy controls. METHODS: We studied SERT activity in 7 patients (22-50 y old) with moderate to severe MDD and 6 healthy controls (24-56 y old) using (123)I-labeled 2-((2-((dimethylamino)methyl) phenyl)thio)-5-iodophenylamine (ADAM) and SPECT brain imaging. Subjects underwent SPECT 4 h after intravenous administration of 185 MBq (5 mCi) of (123)I-ADAM. Images were reconstructed in the axial plane, and region-of-interest demarcations were placed on the midbrain, medial temporal region, and basal ganglia region. RESULTS: (123)I-ADAM binding to SERT in the midbrain was significantly lower (P = 0.01) in MDD patients (1.81 +/- 0.07) than in controls (1.95 +/- 0.13). Age-adjusted (123)I-ADAM binding in the midbrain correlated significantly with scores on the Hamilton Depression Rating Scale (r = 0.82; P = 0.02). A significant negative correlation was observed between (123)I-ADAM SERT binding in the midbrain and age in the healthy control group (r = 0.98; P = 0.0002). SERT binding in the basal ganglia or medial temporal regions of interest did not significantly differ between groups. CONCLUSION: The findings from this preliminary study suggest the possibility of decreased SERT binding in the midbrain region of patients with MDD, with the degree of decrease correlating with the severity of depressive symptoms. There also appears to be an age-related decline in midbrain (123)I-ADAM SERT binding in healthy subjects.     

Phase 1 clinical study of 123I-FP-CIT, a new radioligand for evaluating dopamine transporter with SPECT (I): Biodistribution and absorbed dose]

A Phase 1 clinical study of 123I-FP-CIT, N-(3-fluoropropyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane (123I), developed for evaluation of dopamine transporter (DA-T) by single photon emission computed tomography (SPECT), was performed in 12 healthy male volunteers. No adverse reactions to 123I-FP-CIT (167 MBq) injection were observed. In sequential whole-body images after intravenous injection, the radioactivity was distributed mainly in the liver, abdomen, lungs and brain, and it decreased gradually with time. The radioactivity was excreted mainly in the urine and no prolonged retention of radioactivity was observed in any organs at 2 days post-injection. The radiation absorbed dose of 123I-FP-CIT, calculated on the basis of the pharmacokinetics, was equal to or less than those of other brain diagnostic imaging agents. These results suggest that i.v. injection of 123I-FP-CIT causes no significant problems in terms of its safety, biodistribution or absorbed dose.     

The effects of <Emphasis Type="Italic">d</Emphasis>-amphetamine on extrastriatal dopamine D<Subscript>2</Subscript>/D<Subscript>3</Subscript> receptors: a randomized,double-blind,placebo-controlled PET study with [<Superscript>11</Superscript>C]FLB 457 in healthy subjects

Purpose  The dopamine D₂/D₃ receptor ligand [¹¹C]FLB 457 and PET enable quantification of low-density extrastriatal D₂/D₃ receptors, but it is uncertain whether [¹¹C]FLB 457 can be used for measuring extrastriatal dopamine release. Methods  We studied the effects of d-amphetamine (0.3 mg/kg i.v.) on extrastriatal [¹¹C]FLB 457 binding potential (BP_ND) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. Results  The effects of d-amphetamine on [¹¹C]FLB 457 BP_ND and distribution volume (V_T) in the frontal cortex were not different from those of placebo. Small decreases in [¹¹C]FLB 457 BP_ND were observed only in the posterior cingulate and hippocampus. The regional changes in [¹¹C]FLB 457 BP_ND did not correlate with d-amphetamine-induced changes in subjective ratings of euphoria. Conclusion  This placebo-controlled study showed that d-amphetamine does not induce marked changes in measures of extrastriatal dopamine D₂/D₃ receptor binding. Our results indicate that [¹¹C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans.