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A novel fluorine-18 β-fluoroethoxy organophosphate positron emission tomography imaging tracer targeted to central nervous system acetylcholinesterase.

ABSTRACT: Radiosynthesis of a fluorine-18 labeled organophosphate (OP) inhibitor of acetylcholinesterase (AChE) and subsequent positron emission tomography (PET) imaging using the tracer in the rat central nervous system are reported. The tracer structure, which contains a novel β-fluoroethoxy phosphoester moiety, was designed as an insecticide-chemical nerve agent hybrid to optimize handling and the desired target reactivity. Radiosynthesis of the β-fluoroethoxy tracer is described that utilizes a [(18)F]prosthetic group coupling approach. The imaging utility of the [(18)F]tracer is demonstrated in vivo within rats by the evaluation of its brain penetration and cerebral distribution qualities in the absence and presence of a challenge agent. The tracer effectively penetrates brain and localizes to cerebral regions known to correlate with the expression of the AChE target. Brain pharmacokinetic properties of the tracer are consistent with the formation of an OP-adducted acetylcholinesterase containing the fluoroethoxy tracer group. Based on the initial favorable in vivo qualities found in rat, additional [(18)F]tracer studies are ongoing to exploit the technology to dynamically probe organophosphate mechanisms of action in mammalian live tissues.

SUBMITTER: James SL

PROVIDER: S-EPMC4102964 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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A novel fluorine-18 β-fluoroethoxy organophosphate positron emission tomography imaging tracer targeted to central nervous system acetylcholinesterase.

James Shelly L SL Ahmed S Kaleem SK Murphy Stephanie S Braden Michael R MR Belabassi Yamina Y VanBrocklin Henry F HF Thompson Charles M CM Gerdes John M JM

ACS chemical neuroscience 20140423 7

Radiosynthesis of a fluorine-18 labeled organophosphate (OP) inhibitor of acetylcholinesterase (AChE) and subsequent positron emission tomography (PET) imaging using the tracer in the rat central nervous system are reported. The tracer structure, which contains a novel β-fluoroethoxy phosphoester moiety, was designed as an insecticide-chemical nerve agent hybrid to optimize handling and the desired target reactivity. Radiosynthesis of the β-fluoroethoxy tracer is described that utilizes a [(18)F ...[more]

PMID: 24716794

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Project description:ObjectiveFluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) and PET/CT have been suggested for confirming or excluding musculoskeletal infection but the diagnostic value of this tool for pyogenic spondylitis remains to be confirmed. This meta-analysis was performed to verify the accuracy of 18F-FDG PET and PET/CT in diagnosing suspected pyogenic spondylitis by performing a systematic review and meta-analysis.MethodsWe conducted a comprehensive literature search of PubMed, Embase and Cochrane Library to retrieve diagnostic accuracy studies in which suspected pyogenic spondylitis was assessed with 18F-FDG PET or PET/CT. The pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), summarized receiver operating characteristic curve (sROC) and the area under the sROC (AUC) were calculated by using Stata software.ResultsA total of 18 eligible studies (660 patients) with suspected pyogenic spondylitis were included in the quantitative analysis. 18F-FDG PET and PET/CT illustrated relatively high sensitivity (0.91, 95% CI: 0.84-0.95) and specificity (0.90, 95% CI: 0.79-0.95) for the diagnosis of pyogenic spondylitis. The pooled DOR and AUC were 86.00 (95% CI, 31.00-240.00) and 0.96 (95% CI, 0.94-0.97), respectively. For diagnosing pyogenic spondylitis without previous spine surgery, the pooled sensitivity, specificity, DOR and AUC were 0.93 (95% CI, 0.85-0.97), 0.91 (95% CI, 0.77-0.97), 136 (95% CI, 35-530) and 0.97 (95% CI, 0.95-0.98), respectively. For diagnosing postoperative pyogenic spondylitis, the pooled sensitivity, specificity, DOR and AUC were 0.85 (95% CI, 0.71 to 0.93), 0.87 (95% CI, 0.66 to 0.96), 38 (95% CI, 9 to 167) and 0.92 (95% CI, 0.89 to 0.94), respectively.Conclusion18F-FDG PET and PET/CT presented satisfactory accuracy for diagnosing pyogenic spondylitis. The diagnostic effect of this nuclear imaging method for pyogenic spondylitis without previous spine surgery seems to be better than that for the postoperative ones. However, whether 18F-FDG PET and PET/CT could become a routine in patients with suspected pyogenic spondylitis remains to be confirmed.Level of evidenceLevel I evidence, a summary of meta-analysis.

Dataset Information

A novel fluorine-18 β-fluoroethoxy organophosphate positron emission tomography imaging tracer targeted to central nervous system acetylcholinesterase.

Publications

A novel fluorine-18 β-fluoroethoxy organophosphate positron emission tomography imaging tracer targeted to central nervous system acetylcholinesterase.

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