Abstract
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Objectives: Quantification of imaging with C-11 Rolipram is key to studying Phosphodiesterase IV (PDE IV)in CNS disorders and treatment regimes.
Methods: We have examined R(-)Rolipram and the less active S(+)C-11 Rolipram in healthy humans. The R(-)average specific activity was 322 GBq/micromole and S(+)was 311 GBq/micromole with 3 studied on GE Advance (41±14 years), 2 which had the R(-) and S(+)PET tracer. Nine (31± 8.6 years)were studied with [11C]R(-)Rolipram and 5 received S(+)Rolipram on HRRT. To show specificity aminophylline was infused IV -25 min prior to a 2nd PET at 4 and 7.5 mg/kg. The distribution volume (DV) of S(+)Rolipram was used to estimate free plus nonspecific binding (DVF+NS) in (R-)Rolipram study, and the binding potential (BP) was calculated as DV/DVF+NS-1. The aminophylline blocking effects was measured as percent changes in BP from baseline.
Results: The studies demonstrated reversible binding for both the R (-)and S(+)for multiple brain regions. Using 4 mg/kg aminophylline, there was a reduction in BP of 12% on average in cortical regions using the GE Advance. For 7.5 mg/kg carried out on the HRRT the occupancy was as high as 86% in cortical regions.
Conclusions: These findings not only demonstrate the feasibility of PET imaging in humans, but also document the dose dependant occupancy with aminophylline. Further studies with non-specific PDE IV inhibitors will further help determine the validation of this radiotracer.
- Society of Nuclear Medicine, Inc.