Measuring SSRI occupancy of SERT using the novel tracer [123I]ADAM: a SPECT validation study

Purpose Serotonergic brain regions play a crucial role in the modulation of emotion, and serotonergic dysfunction may contribute to several neurological disorders. [¹²³I]ADAM is a novel SPECT tracer which binds with high affinity to serotonin transporters (SERT). The objective of this study was to compare different methods for the quantification of tracer binding and to develop a simplified single-scan protocol for this tracer, as well as to investigate its potential for characterisation of the transporter occupancy versus plasma concentration curve of a selective serotonin re-uptake inhibitor (SSRI).Methods Dynamic SPECT scans were performed on 16 healthy volunteers after administration of 150 MBq [¹²³I]ADAM. Data were acquired from the time of injection until 5.5 h after injection in 30- or 45-min sessions. Each subject was scanned twice: with and without pre-treatment with the SSRI citalopram in various dosage regimens. The plasma concentration of citalopram (C_p) was determined from venous samples. Images were reconstructed by filtered back-projection with scatter and attenuation correction. Tracer binding was quantified for midbrain, striatum and thalamus using cerebellum as a reference region. Quantification was done by kinetic modelling, graphical analysis and multi-linear regression, as well as by the ratio method, with binding potential (BP₂) as the outcome measure. The SERT occupancy by citalopram was determined relative to the baseline scan for each subject, and the occupancy versus C_p curve was fitted with the E_max model.Results The highest binding of [¹²³I]ADAM was in midbrain (mean baseline BP₂±SD=1.31±0.29), with lower binding in thalamus (0.79±0.16) and striatum (0.66±0.13). There was good agreement between BP₂ values obtained by different quantification methods. Using the ratio method, the best agreement with kinetic modelling was obtained with data from the time interval [200,260] min after injection. The fitting of the midbrain occupancy curve yielded a maximum occupancy of 84% and a plasma concentration required to reach 50% of the maximum of 2.5 ng/ml, with a goodness-of-fit variability of 13% (SD).Conclusion Binding of [¹²³I]ADAM to SERT in midbrain can be quantified with a single scan starting 200 min after injection. However, the variability of estimated occupancy values may be too high for critical assessment of occupancy of SERT by SSRI.     

Computation of tactile object properties requires the integrity of praxic skills

We describe a series of experiments to examine the tactile identification of objects over the course of neurological recovery in a patient with an intracerebral haemorrhage involving the left inferior and superior parietal lobe. Tactile agnosia in this case involved the ipsilesional as well as the contralesional hand, allowing us to observe the effects of dominant parietal lobe damage without the confounding effects of hemiparesis. The findings demonstrate that both apraxia and tactile apperceptive agnosia may result from a unilateral lesion involving the left parietal lobe. The findings further suggest that the computation of macro-geometrical and micro-geometrical tactile object properties is dissociable. Macro-geometrical tactile analysis depends on intact programming of exploratory hand movements, while the role of such movements in micro-geometrical analysis is less clear.     

Factors influencing infant feeding method in an urban community

The benefits of breastfeeding are well established. However, despite this fact, rates of breastfeeding continue to be low, falling far below the goals of Healthy People 2010. Rates are even lower among ethnic minority and low-income women. In this study, we attempt to identify the factors that most influence a mother's choice of infant feeding method in an urban predominately African-American population. Phone interviews of 70 women who delivered full-term infants at an urban tertiary care hospital were conducted in order to explore knowledge, attitudes, and beliefs about breastfeeding of the mothers and that of members of their social support network. Ten mothers (14%) exclusively breastfed. Older, caucasian, and married women were more likely to breastfeed. Breastfeeding mothers reported more partner support as well as more family knowledge about breastfeeding and had more positive attitudes about breastfeeding. Healthcare providers were not directly influential in mother's feeding choice. From this study, we conclude that in this population, the mother's partner and family are most influential in the choice of infant feeding method and, thus, should be included in breastfeeding promotion programs.