caa a22 4500 445377585 CHVBK 20180317143007.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00702-010-0499-z doi (NATIONALLICENCE)springer-10.1007/s00702-010-0499-z MicroPET imaging of ketamine-induced neuronal apoptosis with radiolabeled DFNSH [Elektronische Daten] [X. Zhang, M. Paule, G. Newport, N. Sadovova, M. Berridge, S. Apana, G. Kabalka, W. Miao, W. Slikker Jr., Cheng Wang] Recent reports indicate that 6-12h of ketamine anesthesia can trigger neuronal apoptosis in postnatal day (PND) 7 rats. In vitro, ex vivo, and confocal fluorescent imaging studies suggest that dansyl compounds can accumulate within the cytoplasm of the apoptotic cell. High-resolution positron emission tomography (microPET) imaging has been proposed as a minimally invasive method for detecting apoptosis in the rat brain. Compared with [18F]-labeled annexin V, which binds to externalized phosphatidylserine (PS) on the outer membrane of apoptotic cells, intracellular uptake of the dansylhydrazone of p-fluorobenzaldehyde (DFNSH) may lead to improved target-to-background contrast ratios. In this study, the effect of ketamine on the uptake and retention of [18F]-DFNSH in the rat brain was investigated using microPET imaging. On PND 7, rat pups in the experimental group were exposed, at 2-h intervals, to six subcutaneous injections of ketamine (20mg/kg) and control rat pups received six injections of saline. On PND 35, [18F]-DFNSH (37MBq) was injected into the tail vein of rats and microPET images were obtained over 2h following the injection. Radiolabeled tracer accumulation in the region of interest (ROI) in the frontal cortex was converted into standard uptake values (SUVs). The radiotracer was quickly distributed into the brains of both ketamine- and saline-treated rats. Compared with the control group, the uptake of [18F]-DFNSH was significantly increased in the ROI, frontal cortex area of ketamine-treated rats. In addition, the wash-out duration of the tracer was prolonged in the ketamine-treated animals. This study demonstrates that microPET imaging is capable of distinguishing differences in retention of [18F]-DFNSH in ROI and suggests that this compound may serve as a minimally invasive biomarker of neuronal apoptosis in rodents. Springer-Verlag (outside the USA), 2010 Ketamine nationallicence Apoptosis nationallicence MicroPET nationallicence DFNSH nationallicence Zhang X. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut Paule M. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut Newport G. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut Sadovova N. Toxicologic Pathology Associates, 72079, Jefferson, AR, USA aut Berridge M. 3D Imaging, LLC, 72113, Little Rock, AR, USA aut Apana S. 3D Imaging, LLC, 72113, Little Rock, AR, USA aut Kabalka G. The University of Tennessee, 37920, Knoxville, TN, USA aut Miao W. The University of Tennessee, 37920, Knoxville, TN, USA aut Slikker Jr. W. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut Wang Cheng Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut Journal of Neural Transmission Springer Vienna 118/2(2011-02-01), 203-211 0300-9564 118:2<203 2011 118 702 https://doi.org/10.1007/s00702-010-0499-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00702-010-0499-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang X. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut NATIONALLICENCE 700 1- Paule M. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut NATIONALLICENCE 700 1- Newport G. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut NATIONALLICENCE 700 1- Sadovova N. Toxicologic Pathology Associates, 72079, Jefferson, AR, USA aut NATIONALLICENCE 700 1- Berridge M. 3D Imaging, LLC, 72113, Little Rock, AR, USA aut NATIONALLICENCE 700 1- Apana S. 3D Imaging, LLC, 72113, Little Rock, AR, USA aut NATIONALLICENCE 700 1- Kabalka G. The University of Tennessee, 37920, Knoxville, TN, USA aut NATIONALLICENCE 700 1- Miao W. The University of Tennessee, 37920, Knoxville, TN, USA aut NATIONALLICENCE 700 1- Slikker Jr W. Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut NATIONALLICENCE 700 1- Wang Cheng Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079-9502, Jefferson, AR, USA aut NATIONALLICENCE 773 0- Journal of Neural Transmission Springer Vienna 118/2(2011-02-01), 203-211 0300-9564 118:2<203 2011 118 702 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer