Evaluation of [C-11]R116301 as a PET tracer of the NK1 receptor: A test-retest study in human subjects

Introduction: R116301 is an orally active, potent and selective non-peptide NK1 receptor antagonist. In a previous study [1], size and presence of the specific signal of [C-11]R116301 was demonstrated using a blocking study. Based on the striatum to cerebellum ratio, a specific signal of around 20-50% was found. To assess [C-11]R116301 further as an NK1 receptor ligand, the purpose of the present study was to assess test-retest variability of [C-11]R116301 binding. Methods: Studies were performed in 8 normal controls. Each study consisted of two [C-11]R116301 scans, 5 hours apart. Individual scan sessions consisted of a 2D transmission scan and a 90 minutes dynamic 3D emission scan following intravenous administration of ∼390 MBq [C-11]R116301 [2]. In addition, continuous on-line and discrete manual arterial blood sampling was performed to derive a metabolite corrected arterial plasma input function. A region of interest comprising whole striatum (the structure with the highest density of NK1 receptors) was defined on an individual MRI scan and projected onto both co-registered PET scans. Cerebellum was used as reference tissue. Striatum to cerebellum ratios (60-90 minutes post injection) were used as outcome parameter. In addition, striatum BP was obtained using Receptor Parametric Mapping (RPM), the basis function implementation of the simplified reference tissue model [3]. Data could not be analysed with arterial input compartment models due to severe stickiness of the tracer. Results: Equilibrium was reached relatively early after injection, and striatum to cerebellum ratios were almost identical for the intervals 20-90 and 60-90 minutes. Test-retest Results: of striatum to cerebellum ratios (Table 1) were very tight (range 0.97-1.06), showing an average difference of 3% between scans. However, this ratio contains both specific and non-specific components. For the specific component (i.e. by subtracting 1 from the ratios), the average difference between the two scans was 10% (excluding subject 3, where no specific signal was observed). This was similar to the 9% average difference in BP between the two scans as measured with RPM (Table 1). Conclusion: Test-retest variability of striatum to cerebellum ratios was excellent (3%). Despite the relatively high level of non-specific binding, test-retest variability of specific binding (BP) remained acceptable (10%). The large variation in specific signal between subjects needs to be addressed in future studies.