EVALUATION OF A NITROXYL FATTY-ACID AS LIVER CONTRAST AGENT FOR MAGNETIC-RESONANCE-IMAGING

In this study, we report the synthesis and the evaluation as MRI contr ast agent of a new compound (nitroxyl fatty acid, NFA), where a pyrrol idinoxyl radical (3-carboxy-proxyl, PCA) is linked to a fatty acid moi ety. Fatty acids were selected as vector because they present a high a ffinity for the liver, their efficient cellular uptake being the resul t of a specific interaction with a transmembrane transporter (liver pl asma membrane-fatty acid binding protein). The uptake of H-3-oleic aci d is inhibited after the injection of 1 mmol/kg of NFA, suggesting tha t NFA recognizes the same transmembrane transporter as the natural fat ty acids. The higher relaxivity R1 of NFA in albumin solutions, compar ed with PCA, was explained by the immobilization of the nitroxyl radic al in the protein. MR imaging was performed using T1-weighted images o n mice in order to compare the contrast effect obtained after the inje ction of 1 mmol/kg of radical. The % signal enhancement in the liver 5 min after intravenous injection was 49 +/- 4 and 14 +/- 5 for NFA and PCA, respectively. NFA allowed a better delimitation of some necrotic tumors (Novikoff hepatocarcinoma) due to its preferential uptake by t he nontumorous tissue.