Azapropazone and derivatized EDTA and DTPA complexes as MRI contrast agents

Abstract

<p>Azapropazone is a non-steroidal anti-inflammatory drug (NSAID), that had not been structurally characterized before this work began. The X-ray crystal structure of azapropazone is presented here. The synthesis of several derivatives of azapropazone is outlined. The X-ray crystal structures of the derivatives are presented and described and compared to the structure of azapropazone. The discrepancies in the literature on the previously proposed structures of azapropazone and its derivatives are also discussed. Contrast agents for MRI are necessary for site-specific image enhancement. Potential new agents are presented in this work. The synthesis and characterization of amino acid derivatives of ethylenediaminetetracetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) is described. The amino acids used are the benzyl esters of glycine, phenylalanine, and tyrosine. The relaxivities of the ligands with Gd(III) were determined and compared to the relaxivities of similar complexes in the current literature. The synthesis and characterization of azapropazone derivatives of EDTA and DTPA is described. The possibility of inflammation-site imaging is discussed. The relaxivities of these ligands with Gd(III) was determined and compared to the relaxivities of similar complexes in the current literature. The results of biodistribution studies and single photon emitted computed tomography (SPECT) images of rats injected with the glycine or azapropazone DTPA derivative complexed with ¹¹¹In(III) are described.</p>