Kinetic analysis in human brain of [¹¹C](R)-rolipram, a positron emission tomographic radioligand to image phosphodiesterase 4: A retest study and use of an image-derived input function

[¹¹C](R)-rolipram provides a measure of the density of phosphodiesterase 4 (PDE4) in brain, an enzyme that metabolizes cAMP. The aims of this study were to perform kinetic modeling of [¹¹C](R)-rolipram in healthy humans using an arterial input function and to replace this arterial input in humans with an image-derived input function. Methods: Twelve humans had two injections of [¹¹C](R)-rolipram. An image-derived input function was obtained from the carotid arteries and four blood samples. The samples were used for partial volume correction and for estimating the parent concentration using HPLC analysis. Results: An unconstrained two-compartment model and Logan analysis measured distribution volume V_T, with good identifiability but with moderately high retest variability (15%). Similar results were obtained using the image input (ratio image/arterial V_T=1.00±0.06). Conclusions: Binding of [¹¹C](R)-rolipram to PDE4 can be quantified in human brain using kinetic modeling and an arterial input function. Image input function from carotid arteries provides an equally accurate and reproducible method to quantify PDE4.