title: Neurofunctional imaging of the pancreas utilizing the cholinergic PET radioligand [18F]4-fluorobenzyltrozamicol.
abstract: The pancreas is one of the most heavily innervated peripheral organs in the body. Parasympathetic and sympathetic neurons terminate in the pancreas and provide tight control of endocrine and exocrine functions. The aim of this study was to determine whether the pancreas can be imaged with a radioligand that binds to specific neuroreceptors. Using fluorine-18 4-fluorobenzyltrozamicol (FBT), which binds to the presynaptic vesicular acetylcholine transporter, positron emission tomography scans were performed in four adult mice, two adult rhesus monkeys, and one adult human. In these mammals, the pancreas is intensely FBT avid, with uptake greater than in any other organ at 30, 60, and 90 min. The maximum standardized uptake value (SUV) ratios of pancreas to liver, for example, ranged from 1.4 to 1.7 in rhesus monkeys (mean 1.6; median 1.7) and from 1.9 to 4.7 (mean 3.24; median 3.02) in mice. The maximum SUV ratio of pancreas to liver in the human was 1.8. These data suggest that neuroreceptor imaging of the pancreas in vivo is feasible in animal models and humans. This imaging could allow researchers to interrogate functions under control of the autonomic nervous system in the pancreas, with applications possible in transplanted and native pancreata. Also, as beta cell function is intimately related to parasympathetic cholinergic input, FBT activity in the pancreas may correlate with insulin-producing beta cell mass. This could ultimately provide a method of in vivo imaging in animal models and humans for diabetes research.
authors.affiliation: Nuclear Medicine Section, Department of Radiology, Wake Forest University School of Medicine, Winston-Salem 27157, USA. pbclark@wfubmc.edu
authors.forename: P B
authors.initials: PB
authors.lastname: Clark
authors.forename: H D
authors.initials: HD
authors.lastname: Gage
authors.forename: C
authors.initials: C
authors.lastname: Brown-Proctor
authors.forename: N
authors.initials: N
authors.lastname: Buchheimer
authors.forename: J
authors.initials: J
authors.lastname: Calles-Escandon
authors.forename: R H
authors.initials: RH
authors.lastname: Mach
authors.forename: K A
authors.initials: KA
authors.lastname: Morton
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005464:Fluorobenzenes / Q000493:pharmacokinetics*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D026901:Membrane Transport Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010179:Pancreas / Q000000981:diagnostic imaging* / Q000294:innervation / Q000378:metabolism*; D010880:Piperidines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D011984:Sensory Receptor Cells / Q000000981:diagnostic imaging / Q000378:metabolism; D013045:Species Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D005464:Fluorobenzenes; D026901:Membrane Transport Proteins; D010880:Piperidines; D019275:Radiopharmaceuticals; C493459:SLC18A3 protein, human; C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C087277:4-fluorobenzyltrozamicol