Synthesis and evaluation of indomethacin ester and amide derivatives for imaging brain COX-2

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The aim of this study is to find suitable radioligands for PET studies which are targeted COX-2 in brain. Indomethacin derivatives are selected as a ligand expecting brain uptake.We prepared and evaluated 11C-labeled ester and amide analogs derived from indomethacin, with different lipophilicities. The in vivo behavior of all radiotracers in mice is characterized by low brain uptake and fast metabolic susceptibility. However, this result suggesting that the lipophilicity could be used to predict the BBB permeability for derivatives of indomethacin and related compounds. Although further structural refinement of the radiotracers is necessary to achieve better enhancement of brain uptake and sufficient metabolic stability, current results will be guiding the design of COX-2 selective radiotracers.