First Evaluation of [11C]R116301 as an In Vivo Tracer of NK1 Receptors in Man

PURPOSE: NK1 receptors have been implicated in various neuropsychiatric and other disorders. R116301 is a selective NK1 receptor antagonist. In this pilot study, [(11)C]R116301 was evaluated as a potential positron emission tomography (PET) ligand for the NK1 receptor. PROCEDURES: Two dynamic PET studies were performed in three normal volunteers before and after a blocking dose of aprepitant. Data were analyzed using striatum to cerebellum standardized uptake value (SUV) ratios. RESULTS: Baseline SUV ratios at 60-90 min after injection ranged from 1.22 to 1.70. Following aprepitant administration, this specific signal was completely blocked. Aprepitant administration did not significantly affect uptake in cerebellum, confirming the absence of NK1 receptors in cerebellum. CONCLUSION: These preliminary results indicate that [(11)C]R116301 has potential as a radioligand for in vivo assessment of NK1 receptors in the human brai

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