Novel Pet Ligand [18F]PF974 can Measure Inflammatory Activation of Phosphodiesterase-4B (PDE4B) in Rat Brain

The cyclic adenosine monophosphate (cAMP) theory of depression posits that low cAMP signaling predisposes to major depressive episodes. Increased cAMP signaling phosphorylates and activates phosphodiesterase-4 (PDE4), which increases radioligand affinity tenfold; thus, cAMP signaling can be indirectly detected by radioligand binding of PDE4. Inhibition of the PDE4B subtype has antidepressant-like properties in animals and anti-inflammatory properties in animals and humans. The novel positron emission tomography (PET) radioligand PF974 was developed to visualize PDE4B in vivo. This study sought: 1) to evaluate PF974 as a dynamic biomarker specific for PDE4B by imaging its distribution and pharmacokinetics in rats; 2) to determine whether inflammatory changes affect PDE4B binding; and 3) whether these changes could be measured in living animals using PF974.