TY - JOUR T1 - In Vivo Imaging of Human Acetylcholinesterase Density in Peripheral Organs Using <sup>11</sup>C-Donepezil: Dosimetry, Biodistribution, and Kinetic Analyses JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1818 LP - 1824 DO - 10.2967/jnumed.114.143859 VL - 55 IS - 11 AU - Trine Gjerløff AU - Steen Jakobsen AU - Adjmal Nahimi AU - Ole L. Munk AU - Dirk Bender AU - Aage K.O. Alstrup AU - Karina H. Vase AU - Søren B. Hansen AU - David J. Brooks AU - Per Borghammer Y1 - 2014/11/01 UR - http://jnm.snmjournals.org/content/55/11/1818.abstract N2 - Brain cholinergic function has been previously studied with PET but little effort has been devoted to imaging peripheral organs. Many disorders, including diabetes and Parkinson disease, are associated with autonomic dysfunction including parasympathetic denervation. Nonneuronal cholinergic signaling is also involved in immune responses to infections and in cancer pathogenesis. 5-11C-methoxy-donepezil, a noncompetitive acetylcholinesterase ligand, was previously validated for imaging cerebral levels of acetylcholinesterase. In the present study, we explored the utility of 11C-donepezil for imaging acetylcholinesterase densities in peripheral organs, including the salivary glands, heart, stomach, intestine, pancreas, liver, and spleen. Methods: With autoradiography, we determined binding affinities and levels of nonspecific 11C-donepezil binding to porcine tissues. Radiation dosimetry was estimated by whole-body PET of a single human volunteer. Biodistribution and kinetic analyses of 11C-donepezil time–activity curves were assessed with dynamic PET scans of 6 healthy human volunteers. A single pig with bacterial abscesses was PET-scanned to explore 11C-donepezil uptake in infections. Results: Autoradiography showed high 11C-donepezil binding (dissociation constant, 6–39 nM) in pig peripheral organs with low nonspecific signal. Radiation dosimetry was favorable (effective dose, 5.2 μSv/MBq). Peripheral metabolization of 11C-donepezil was low (&gt;90% unchanged ligand at 60 min). Slow washout kinetics were seen in the salivary glands, heart, intestines, pancreas, and prostate. A linear correlation was seen between 11C-donepezil volumes of distribution and standardized uptake values, suggesting that arterial blood sampling may not be necessary for modeling uptake kinetics in future 11C-donepezil PET studies. High standardized uptake values and slow washout kinetics were seen in bacterial abscesses. Conclusion: 11C-donepezil PET is suitable for imaging acetylcholinesterase densities in peripheral organs. Its uptake may potentially be quantitated with static whole-body PET scans not requiring arterial blood sampling. We also demonstrated high 11C-donepezil binding in bacterial abscesses. We propose that 11C-donepezil PET imaging may be able to quantify the parasympathetic innervation of organs but also detect nonneuronal cholinergic activity in infections. ER -