Studies On The Dry Separation Of Medical Isotopes ²¹¹At,⁹⁹Mo And ^99MTc Produced By Accelerators

Cancer,as one of the most important causes of human death,the incidence and death cases are increasing yearly.According to the estimation from the World Health Organization（WHO）,global cancer cases will increase by 60%by 2040.Therefore,the research on cancer diagnosis and treatment plays an important role in human health and survival.With the development of nuclear medicine,radioisotopes are increasingly used in the diagnosis and treatment of various diseases,especially in cancer.²¹¹At has attracted much attention as a promisingα-particle emitting radioisotopes for targeted radiotherapy,and many related drugs have been involved into clinical trials.Many studies on ²¹¹At have been conducted in developed countries such as Europe,USA,and Japan.But due to the availability issue of accelerator in China,only the researcher in Sichuan University has been engaged in related research for a long time.^99mTc is the most widely used nuclide in medical imaging,accounting for 80%of the world’s medical isotope usage.^99mTc mainly comes from the ^99mTc-⁹⁹Mo generator.⁹⁹Mo,as the mother nuclide used in the ^99mTc-⁹⁹Mo generator,is mostly produced from the fission of high-enriched uranium in nuclear reactors.However,the supply of ⁹⁹Mo is extremely fragile,facing some problems such as reactor decommissioning,high risk of nuclear proliferation,and large volumes of radioactive waste.The development of nuclear medicine in our country is faced with a serious dilemma because our clinical medical isotopes are basically imported.Therefore,it is urgent to find an alternative for⁹⁹Mo production.In order to solve the problem of the medical radioisotopes supply in our country,this work explores and studies the production of medical isotopes ²¹¹At,⁹⁹Mo,and ^99mTc.It focuses on testing the accelerator-based production method and the following dry separation method.Firstly,the production process of ²¹¹At was conducted.²¹¹At was produced by irradiating the Bi target withαbeam provided by the Chinese Accelerator Driven Sub-critical System（ADS）Front-end Demo Linac（Linac）at Institute of Modern Physics,Chinese Academy of Sciences（IMP,CAS）.The whole process of ²¹¹At production was systematically investigated,including accelerator irradiation targets,dry distillation separation of ²¹¹At,and ²¹¹At quality analysis.The results show that ²¹¹At can be rapidly separated at 850°C with oxygen as the carrier gas,and then collected by chloroform or ethanol.The total recovery rate was up to 78.53%.The chloroform solution containing²¹¹At can be dried by gas,and the ²¹¹At with high specific activity was obtained,which is convenient for labeling.The content of extremely toxic by-product ²¹⁰At(²¹⁰Po)was also investigated.The results show that when the incident particle energy is lower than28.2 Me V,the value of N(²¹⁰At)/N(²¹¹At)is lower than 10^-5.In addition,the ²¹¹At monoclonal antibody labeling experiment was carried out join with Sichuan University,and the labeling rate was 94.86%,which confirmed the feasibility of the process and the quality of the product could meet the requirements of the labeling experiment.Secondly,two production methods of ⁹⁹Mo were studied.One method is the production of ⁹⁹Mo by irradiating ⁹⁶Zr with alpha particles provided by Riken,Japan.The preparation of ⁹⁹Mo by alpha particles irradiating zirconia and zirconium carbide and its dry separation process are mainly investigated.The results show that the zirconium carbide target can withstand higher beam than zirconia because of its higher thermal conductivity,while the zirconia target is more conducive to the recycling of the target material.More than 80%of ⁹⁹Mo can be separated from the zirconia target at a high temperature above 1250°C with moist oxygen as the reaction atmosphere for more than 80 minutes.Another method is the production ⁹⁹Mo by irradiating ^natU with proton provided by the linear accelerator.The preparation of the UO₂ target,irradiation of UO₂target,and its dry separation process were mainly investigated.The results show that dense UO₂ targets can be sintered below 1400°C by micro-oxidation sintering.After irradiation,the UO₂ target is firstly transformed into powdered U₃O₈ under the action of oxygen at 450°C,and then more than 90%of ⁹⁹Mo can be separated from U₃O₈ with moist oxygen as the reaction atmosphere at a high temperature above 1200°C for more than 2 h.The above results confirm that the two methods for the production of ⁹⁹Mo are feasible and they could be alternative technologies.Thirdly,a production method of ^99mTc was studied.The ^99mTc was produced by irradiating ¹⁰⁰Mo with proton provided by Linac accelerator at IMP.The preparation of the metal molybdenum target,accelerator irradiation of ¹⁰⁰Mo targets,and its dry separation process were tested.The results show that dense molybdenum targets can be sintered at 1550°C.After irradiation,the molybdenum target was first rapidly converted to the corresponding oxide at a temperature above 800°C,and then ^99mTc₂O₇ can dissolve selectively using normal saline or ammonia.In addition,the recovery of ¹⁰⁰Mo is also explored,and the（NH₄）₂Mo O₄ is converted to molybdenum by thermal decomposition and reduction.By conducting above research work,the accelerator-based production of medical radioisotopes ²¹¹At,⁹⁹Mo,and ^99mTc and their dry separation process were successfully achieved,which provided basic experimental data and experience for scale production of ²¹¹At and the further study of new production methods of ⁹⁹Mo/^99mTc.