title: A minimally invasive, translational biomarker of ketamine-induced neuronal death in rats: microPET Imaging using 18F-annexin V.
abstract: It has been reported that suppression of N-methyl-D-aspartate (NMDA) receptor function by ketamine may trigger apoptosis of neurons when given repeatedly during the brain growth spurt period. Because microPET scans can provide in vivo molecular imaging at sufficient resolution, it has been proposed as a minimally invasive method for detecting apoptosis using the tracer (18)F-labeled annexin V. In this study, the effect of ketamine on the metabolism and integrity of the rat brain were evaluated by investigating the uptake and retention of (18)F-fluorodeoxyglucose (FDG) and (18)F-annexin V using microPET imaging. On postnatal day (PND) 7, rat pups in the experimental group were exposed to six injections of ketamine (20 mg/kg at 2-h intervals) and control rat pups received six injections of saline. On PND 35, 37 MBq (1 mCi) of (18)F-FDG or (18)F-annexin V was injected into the tail vein of treated and control rats, and static microPET images were obtained over 1 (FDG) and 2 h (annexin V) following the injection. No significant difference was found in (18)F-FDG uptake in the regions of interest (ROIs) in the brains of ketamine-treated rats compared with saline-treated controls. The uptake of (18)F-annexin V, however, was significantly increased in the ROI of ketamine-treated rats. Additionally, the duration of annexin V tracer washout was prolonged in the ketamine-treated animals. These results demonstrate that microPET imaging is capable of distinguishing differences in retention of (18)F-annexin V in different brain regions and suggests that this approach may provide a minimally invasive biomarker of neuronal apoptosis in rats.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Newport
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Zou
authors.forename: Natalya
authors.initials: N
authors.lastname: Sadovova
authors.forename: Marc S
authors.initials: MS
authors.lastname: Berridge
authors.forename: Scott M
authors.initials: SM
authors.lastname: Apana
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Hanig
authors.forename: William
authors.initials: W
authors.lastname: Slikker
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
mesh_terms: D000778:Anesthetics, Dissociative / Q000633:toxicity*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism*; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000778:Anesthetics, Dissociative; D017304:Annexin A5; D015415:Biomarkers; D005462:Fluorine Radioisotopes; D007649:Ketamine