RT Journal Article
SR Electronic
T1 Caffeine Occupancy of Human Cerebral A<sub>1</sub> Adenosine Receptors: In Vivo Quantification with <sup>18</sup>F-CPFPX and PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1723
OP 1729
DO 10.2967/jnumed.112.105114
VO 53
IS 11
A1 David Elmenhorst
A1 Philipp T. Meyer
A1 Andreas Matusch
A1 Oliver H. Winz
A1 Andreas Bauer
YR 2012
UL http://jnm.snmjournals.org/content/53/11/1723.abstract
AB Caffeine is the neuroactive agent in coffee and tea and is a broadly consumed stimulant. It is a nonselective antagonist of the neuromodulator adenosine and, if applied in commonly consumed doses, evokes its stimulating effects through the blockade of adenosine receptors. 18F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (18F-CPFPX) has been established as a highly selective and affine PET ligand for the A1 adenosine receptor (A1AR). The objective of the present study was to visualize and quantify the in vivo occupancy of the human cerebral A1AR by caffeine using 18F-CPFPX and PET. Methods: Fifteen subjects (age range, 24–68 y) underwent a 140-min bolus–plus–constant-infusion PET experiment after at least 36 h of caffeine abstinence. Metabolite-corrected blood data were used to calculate steady-state distribution volumes (VT) during the baseline condition of the scan between 70 and 90 min. Subsequently, subjects received a 10-min infusion of varying concentrations (0.5–4.3 mg/kg of body weight) of caffeine at 90 min. Occupancy VT of the A1AR was thereafter estimated using data acquired between 120 and 140 min. Occupancy levels were calculated using the Lassen plot, from which the inhibitory concentrations of 50% were derived. Plasma levels of caffeine were determined at regular intervals. One subject received an intravenous vehicle as a placebo. Results: Caffeine displaced 5%–44% of 18F-CPFPX binding in a concentration-dependent manner. There was no change of radioligand binding after the administration of placebo. Half-maximal displacement was achieved at a plasma caffeine concentration of 67 μM, which corresponds to 450 mg in a 70-kg subject or approximately 4.5 cups of coffee. Conclusion: Given a biologic half-life of about 5 h, caffeine might therefore occupy up to 50% of the cerebral A1AR when caffeinated beverages are repeatedly consumed during a day. Furthermore, the present study provides evidence that 18F-CPFPX PET is suitable for studying the cerebral actions of caffeine, the most popular neurostimulant worldwide.