Synthesis of tri-alkyl-phosphine oxide radio-labelled by phosphorus-32. Study of the biodistribution in healthy mice following injection in hepatic artery

The Lipiodol, a mixture of fatty esters radiolabelled by iodine-131 is used in treating primitive hepatic tumors. Dosimetric evaluation of the treatments by Lipiodol brings to light an important limitation due to intrinsic characteristics of the radioactive emissions of iodine-131. Actually, the energy of β (600 keV) and γ (360 keV) emissions is a little weak to obtain a deep radiobiological efficiency. We have suggested replacing iodine-131 by a pure β emitter, the phosphorus-32, the β emission energy of whose is 1.7 MeV. We have established a simple method of accessing a phosphorated fatty compound radiolabelled by P-32, starting from the labelled phosphoric acid, H3*PO4, the unique phosphorylation agent radiolabelled by P-32 on market in France. Our synthesis implies two stages. The first one is an exchange reaction between the phosphorus of H3*PO4 and that of cool POCl3. The second one is the reaction of POCl3 with a fatty chain organo-magnesian. So, we merely obtained a fatty compound radiolabelled by phosphorus-32, with a satisfying specific activity. The compound has been tested on several healthy mice by injection in hepatic artery. A study of the biodistribution has been conducted, on one side by counting the radioactivity in the principal organs and by autoradiography, on the other side. The results at different time intervals reveal the accumulation of the product at the level of liver and lungs (26.90% and 2.26% after 24 h, respectively). The elimination of the compound is effected by digestive way as in case of Lipiodol, via the stomach and colon (8.89% and 39.01% after 24 h, respectively)