- Radiosynthesis and in Vivo and ex Vivo Evaluation of Isomeric [11C]-methoxy Analogs of Nimesulide as Brain Cyclooxygenase-2-Targeted Imaging Agents
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Our previous studies identified that nimesulide analogs which bear a methoxy substituent at the paraposition of the phenyl ring could be potential radiotracer candidates for detecting disorders related to cyclooxygenase-2 (COX-2) expression and activity in vivo using positron emission tomography (PET) in the brain. The present study was conducted to evaluate the in vivo characteristics of 11C-labeled para-methoxy nimesulide ([11C]1d) as a brain COX-2-targeted imaging agent compared to other isomeric methoxy analogs of nimesulide ([11C]1b and [11C]1c). [11C]1b–d were synthesized with reasonable yield and purity by the methylation of the O-desmethyl precursor with [11C]methyl triflate in the presence of NaOH at room temperature. We performed in vivo biodistribution analysis, brain PET imaging, ex vivo autoradiography, and metabolite analysis in mice. The uptake of [11C]1b–d was lower in the brain than in other tissues, including in the blood, and both [11C]1c and [11C]1d were rapidly metabolized. However, [11C]1d showed a small, but significant, specific signal and heterogeneous distribution in the brain. In vivo evaluation suggested that [11C]1d might correlate with COX-2 expression in the brain. Given its instability in vivo, [11C]1d seems unsuitable as a brain-COX-2 radioimaging agent. Further structural refinement of these radiotracers is necessary to enhance their uptake in the brain and to achieve sufficient metabolic stability.
- Saito, Yohei,Tago, Tetsuro,Toyohara, Jun,Yamamoto, Fumihiko,Yamamoto, Yumi
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- A total synthesis of 4-hydroxynimesulide
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4-Hydroxynimesulide, a unique metabolite of Nimesulide has been synthesized by the formation of 4-methoxynimesulide and its subsequent demethylation with aq. HBr-AcOH/anhyd. AlCl3-CH2Cl2.
- Singh, Parmjeet,Singh, Amarjit,Sharma
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p. 1263 - 1264
(2007/10/03)
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- Biomimetic reduction of nimesulide with NaBH4 catalyzed by metalloporphyrins.
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The biomimetic reduction of anti-inflammatory drug, nimesulide (1) with sodium borohydride catalyzed by 5,10,15,20-tetraarylporphyrinatoiron(III) chlorides [TAPFe(III)Cl] has been studied in organic solvents under anaerobic and aerobic conditions.
- Chauhan, Shive Murat Singh,Kandadai, Srinivas Appan,Kumar, Anil
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p. 1421 - 1422
(2007/10/03)
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