Assessing the Optimal Time Point for the Measurement of Extrastriatal Serotonin Transporter Binding with ¹²³I-FP-CIT SPECT in Healthy, Male Subjects

Abstract

123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl) nortropane ( 123 I-FP-CIT) is commonly used to assess the dopamine transporter in the striatum. However, recent studies suggest that this tracer may be used also to assess binding to monoamine transporters in the midbrain or diencephalon, which may reflect predominantly serotonin transporter (SERT) binding. However, it is still unclear at what time point after injection SPECT should be performed for optimal assessment of SERT with 123 I-FP-CIT. Therefore, we examined the time course of extrastriatal 123 I-FP-CIT binding. Methods: Nineteen healthy, male subjects were included, and SPECT images were acquired up to 3 h after 123 I-FP-CIT injection. Region-of-interest analysis was performed, and specific-to-nonspecific binding ratios were calculated. Results: Specific-to-nonspecific 123 I-FP-CIT binding ratios in the midbrain and diencephalon were significantly higher 2 h after injection than 1 h after injection and remained stable between 2 and 3 h after injection. Conclusion: The optimal time frame for assessing 123 I-FP-CIT binding to extrastriatal SERT is between 2 and 3 h after injection of the tracer. In 2000, the radiotracer 123 I-N-v-fluoropropyl-2b-carboxymethoxy-3b-(4-iodophenyl)nortropane ( 123 I-FP-CIT) was registered in Europe to assess striatal dopamine transporter (DAT) binding, and it is now commonly used to study the integrity of nigrostriatal dopaminergic neurons in vivo (1). Recently, the same tracer was licensed in the United States. The optimal time point for measuring striatal DAT is between 3 and 6 h after bolus injection of 123 I-FP-CIT (2).In vitro studies showed a high affinity of 123 I-FP-CIT for the DAT. However, this tracer also has a moderate affinity for the serotonin transporter (SERT) (3). Indeed, in healthy controls we showed that, after administration of the selective serotonin reuptake inhibitor paroxetine, 123 I-FP-CIT binding was significantly blocked in the SERT-rich midbrain and diencephalon (4). Likewise, another recent study showed that thalamic binding of 123 I-FP-CIT could be blocked by the selective serotonin reuptake inhibitor citalopram (5). The relative anatomic segregation between striatal DAT and extrastriatal SERT binding sets the condition for 123 I-FP-CIT SPECT studies to examine also SERT in vivo. Interestingly, recent clinical FP-CIT SPECT studies showed not only loss of striatal DAT but also loss of midbrain SERT binding in dementia with Lewy bodies and in Parkinson patients with depression (6,7). In these 2 studies, 123 I-FP-CIT binding in SERT-rich areas was measured 3 h after injection, but it is not known whether this time point is optimal for assessing FP-CIT binding to SERT.Abi-Dargham et al. studied 4 healthy controls and showed that peak specific 123 I-FP-CIT binding in the midbrain occurred at 72 6 37 min after injection, followed by slow washout (3). In a previous study, we measured SERT binding in the midbrain and diencephalon only at 1 and 3 h after injection of 123 I-FP-CIT (4). These preli...

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