الفهرس | Only 14 pages are availabe for public view |
Abstract Auger electron emitters provide a tool for radiotherapy with low doses of radiations. The pharmacological effect of these Auger electron emitters have been proven by many authors as a radiotoxic agents. Auger emitters produce electrons of low energy deposited near the site of their origin. This energy was sufficient to produce double strand break and hence, inhibit DNA synthesis. Their action is restricted to be only intracellular. Iodine-125 was the famous Auger electron emitter’s radioisotope and the most used one for in vivo as well in vitro studies. This work was conducted to study the radiotherapeutic effect of iodine-125 in vivo on tumor bearing mice and in vitro on EAC cells. The study was also performed to find a model to deliver Auger electron emitters (125I) to tumor cells. This was obtained by labeling of folic acid and nimesulide with iodine-125 to give new therapeutic radiopharmaceuticals that produce their pharmacological action through high tumor targeting ability. Radiolabeling of folic acid and nimesulide with iodine should be performed with high radiochemical yield as to insure that the biological behavior belongs to the radiolabeled compounds not to the free iodide. This because these labeled compound have the ability to deliver the radioisotope to the tumor site to produce the pharmacological effect. It was shown that folic acid and nimesulide were labeled successfully with iodine-125 via direct electrophilic substitution using chloramines-T as an oxidizing agent. It was found that 500 μg and 300 μg of chloramine-T was required respectively for labeling of folic acid and nimesulide. One mg folic acid was used to obtain maximum radiochemical yield (97.6%) while two hundreds μg nimesulide were enough to obtain maximum radiochemical yield (95.1%). The optimum reaction temperature for achieving a maximum radiochemical yield for folic acid and nimesulide is ambient temperature. The reaction medium pH should be 9 for folic acid and 7 for nimesulide. Folic acid radioiodination reaction takes 30 minutes to reach a maximum radiochemical yield while radioiodination of nimesulide takes only one minute to give maximum radiochemical yield. The in vitro stability of both radiolabeled compounds showed that they are stable and no significant change in radiochemical yield up to 48 h post labeling. |