U.S. soldiers' appraisal and experience of the Kosovo peacekeeping mission is described. Using a prospective design, we evaluated the prevalence, severity, and predictors of several mental health outcomes at redeployment. We found that peacekeepers frequently were exposed to potentially traumatizing and other stressful events while in Kosovo, but on average, their appraisal of those events was moderate. Postdeployment psychopathology was also low--soldiers endorsed more severe mental health difficulties at predeployment, which suggests anticipatory negative affect. After controlling for the impact of predeployment stressors, we examined the contribution of potentially traumatizing events, general overseas military duty stressors, negative aspects of peacekeeping roles, and generic positive military experiences, including morale, to explain variance in four outcomes: post-traumatic stress disorder, depression, hostility and aggression problems, and problems with alcohol abuse. Findings indicate that hostility and drinking may be more chronic problems that emerge during stressful times, whereas depression and post-traumatic stress disorder symptoms may be more apt to fluctuate and are associated with potentially traumatizing experiences during peacekeeping. The implications and limitations of the study are discussed.
A novel series of ligands with substitutions at the 5-position on phenyl ring A and at the 4'-position on phenyl ring B of 2-(2'-((dimethylamino)methyl)-4'-(fluoroalkoxy)phenylthio)benzenamine (4'-2-fluoroethoxy derivatives 28-31 and 4'-3-fluoropropoxy derivatives 40-42) were prepared and tested as serotonin transporter (SERT) imaging agents. The new ligands displayed high binding affinities to SERT (Ki ranging from 0.03 to 1.4 nM). The corresponding 18F labeled compounds, which can be prepared readily, showed excellent brain uptake and retention after iv injection in rats. The hypothalamus region showed high uptake values between 0.74% and 2.2% dose/g at 120 min after iv injection. Significantly, the hypothalamus to cerebellum ratios (target to nontarget ratios) at 120 min were 7.8 and 7.7 for [18F]28 and [18F]40, respectively. The selective uptake and retention in the hypothalamus, which has a high concentration of SERT binding sites, demonstrated that [18F]28 and [18F]40 are promising positron emission computed tomography imaging agents for mapping SERT binding sites in the brain.
Results-PET image analysis showed varying levels of SERT binding reduction (rat #1 = −11%, rat #2 = −4%, rat #3 = −43%; n = 2) and a clear and definitive loss of VMAT2 binding (rat #1 = −87%, rat #2 = −72%, and rat #3 = −91%; n = 1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (PCA, p-chloroamphetamine) showed a significant reduction of uptake in the cortex and hypothalamus regions of the brain.
Conclusion-The
The results of the biological studies and the ease of radiosynthesis with moderately good radiochemical yield (RCY=10-35%) make [(18)F]1 an excellent candidate for SERT PET imaging.
PET of the serotonin transporter (SERT) in the brain is a useful tool for examining normal physiologic functions as well as disease states involving the serotonergic system. The goal of this study was to further develop and refine a series of 49-fluoroalkoxy-substituted, 18 F-radiolabeled SERT imaging agents. 2-(29-((Dimethylamino)methyl)-49-(4-18 F-fluorobutoxy)phenylthiol)-benzenamine (3) and 2-(29-((dimethylamino)methyl)-49-(5-18 Ffluoropentoxy)phenylthiol)benzenamine (4) were synthesized and evaluated along with 2 previously reported compounds of this series, 2-(29-((dimethylamino)methyl)-49-(2-18 F-fluoroethoxy)-phenylthiol)benzenamine (1) and 2-(29-((dimethylamino)methyl)-49-(3-18 F-fluoropropoxy)phenylthiol)benzenamine (2). Methods: The in vitro binding affinities of compounds 3 and 4 were determined in monoamine transporter-transfected LLC-PK 1 cell homogenates. In vivo localization of the respective 18 F-labeled compounds was evaluated by biodistribution studies in male Sprague-Dawley rats. Compound 3 was selected for further examination by autoradiographic and PET studies in rats. Results: The corresponding mesylate precursors of 3 and 4 were radiolabeled with 18 F within 75-90 min. Radiochemical yield was 6%235%, specific activity was 15-170 GBq/mmol, and radiochemical purity was greater than 97% (end of synthesis). The compounds showed subnanomolar binding affinities for SERT (inhibition constants, 0.51 and 0.76 nM, respectively), had brain uptake at 2 min of 1.25 and 0.68 percentage injected dose per gram, respectively, and possessed high target-to-nontarget (hypothalamus-to-cerebellum) ratios at 120 min after injection (6.51 and 5.70, respectively). Autoradiographic studies of 18 F-3 showed selective localization in SERT-rich brain regions. PET studies of 18 F-3 showed clear localization in the midbrain, thalamus, and striatum. Conclusion: This compound series was found to have potential for producing a suitable 18 F-radiolabeled PET radiotracer for SERT. Compound 4, the pentoxy derivative, had the lowest brain uptake and target-to-nontarget ratio. Compound 3, the butoxy derivative, had a lower target-to-nontarget ratio than compounds 1 (ethoxy derivative) and 2 (propoxy derivative). Compounds 1 and 2 both hold promise as SERT radioimaging agents, but because of cost limitations, only compound 2 will be evaluated in further studies.
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