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

• Published in: NeuroImage (Orlando, Fla.) Vol. 54; no. 3; pp. 1903 - 1909
• Main Authors: Zanotti-Fregonara, Paolo, Zoghbi, Sami S., Liow, Jeih-San, Luong, Elise, Boellaard, Ronald, Gladding, Robert L., Pike, Victor W., Innis, Robert B., Fujita, Masahiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2011; Elsevier Limited
• Subjects: Adult; Algorithms; Brain - anatomy & histology; Brain - enzymology; Brain research; Cerebral Arteries - diagnostic imaging; Cerebral Arteries - physiology; Compartment model; Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism; Electrocardiography; Female; Human subjects; Humans; Image Processing, Computer-Assisted; Image-derived input function; Kinases; Least-Squares Analysis; Logan plot; Magnetic Resonance Imaging; Male; Metabolite-corrected arterial input function; Methods; Nonlinear Dynamics; Phosphodiesterase 4; Plasma; Plasma - physiology; Positron-Emission Tomography - methods; Radiopharmaceuticals - blood; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Reference Standards; Reproducibility of Results; Rolipram - blood; Rolipram - chemical synthesis; Rolipram - pharmacokinetics; Studies; Test retest reproducibility; Veins & arteries; Phosphodiesterase 4; Compartment model; Test retest reproducibility; Metabolite-corrected arterial input function; Logan plot; Image-derived input function
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2010.10.064

[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. 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. An unconstrained two-compartment model and Logan analysis measured distribution volume VT, with good identifiability but with moderately high retest variability (15%). Similar results were obtained using the image input (ratio image/arterial VT=1.00±0.06). 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. ►Binding of [11C](R)-rolipram to phosphodiesterase 4 can be reliably quantified in human brain using a two-tissue compartment model and a Logan plot. ►[11C](R)-rolipram binding has a moderate test-retest variability of about 15%. ►An image-derived input function method, using the PET blood pool of carotid arteries, gives almost identical distribution volumes to those obtained with invasive arterial blood sampling. ►This image input method allows not only the estimation of the whole-blood time activity curve, like all the methods described in the literature up to now, but also the estimation of the parent concentration in plasma.