Preparation of ¹³¹I- lipiodol and fabrication of prototype semi-automated module

Primary hepatocellular carcinoma (HCC) is the most common tumor with its highest incidence in the developing world. Lipiodol (Iodinated ester of poppy seed oil) exhibits longer retention in hepatoma compared to normal liver when injected directly into the hepatic artery. Intra-arterial injection of ¹³¹I-Lipiodol delivers very high radiation dose to tumor with minimal damage to adjacent normal tissue making ¹³¹I lipiodol an effective radio-therapeutic agent. The work was taken up with the aim to develop procedures and design and fabricate a semi-automated module suitable for synthesis of clinical grade ¹³¹I lipiodol. ¹³¹I lipiodol was prepared by isotopic exchange reaction of ionic ¹³¹I and organic iodine. The radiolabeling parameters were standardized. The reaction was carried out by extracting ¹³¹I in ethanol followed by iodine exchange in lipiodol. The effect of temperature was studied for labeling efficiency. Radiochemical evaluation was carried out using ITLC, using 85% methanol. The semi-automated synthesis module was designed based on optimized reaction parameters. The small sized module suitable to be placed in hot-cell or sufficiently shielded fume-hood is fabricated using reactant compatible solenoid valves and tubings. Results and Discussion: The radiolabeling yield was found to be dependent on drying conditions when ethanol was used as a solvent for exchange reaction. Consistent yield of around 60% was obtained under optimised conditions. The radiochemical purity of ¹³¹I- Lipiodol was >95% as determined by ITLC. The product was stable for 1 week when stored in dark at ambient temperature. The fabricated semi-automated module will enable remote and precise liquid transfers as well as controlled heating with less than 5% variation. Pharmaceutically pure and safe product can be prepared from the module by terminal membrane filtration in sterile and pyrogen free product vial. ¹³¹I-Lipiodol was successfully prepared in good yields and >95% purity with adequate stability. The indigenous fabrication of semi automated prototype module is an important contribution towards preparation of therapeutic radiopharmaceutical under GMP. (author)