Study of the Inhibition of [11C]R-rolipram Binding to Brain Phosphodiesterase - 4 (PDE-4) by HT-0712

A PET Study: Single-dose, Open-label Study of the Inhibition of [11C]R-rolipram Binding to Brain Phosphodiesterase - 4 (PDE-4) by HT-0712

This Positron Emission Tomography (PET) imaging study is designed to explore the relationship between HT-0712 dose level and inhibition of brain phosphodiesterase-4 activity, in order to optimize the dosage regimens utilized in subsequent trials.

The objective of this project is to demonstrate the inhibition of human brain PDE4 by HT-0712, by measuring the inhibition of [11C]R-rolipram binding, a radiotracer which also binds to and inhibits PDE4. Plasma samples will be drawn to determine if there is a relationship between plasma pharmacokinetics of HT-0712 and its pharmacodynamic effect, as determined through the inhibition of [11C]R-rolipram binding in the brain.

Main Inclusion Criteria:

• Healthy, elderly, non-smoking men and post-menopausal women
• Ability to give informed consent

Main Exclusion Criteria:

• Current or history of uncontrolled hypertension, major depression, Parkinson's disease, stroke and diabetes.
• Physical or behavioral conditions that may alter brain function