Preparation Of The Medical Isotope ⁶⁸Ge Based On Accelerator And Development Of ⁶⁸Ge/⁶⁸Ga Generator

Cancer（or malignant tumor）has become one of the greatest threats to human health all over the world.So,the early diagnosis and evaluation of tumors is of great importance to the treatment of cancer and malignant tumor.Nuclear image technique has become one of the detection means for the early diagnosis of tumors because of real-time,high accuracy and high sensitivity…Nuclear image technique mainly consisted of Positron Emission Tomography（PET）and Single Photo Emission Computed Tomography（SPECT）.PET,a biomedical imaging device with remarkably higher accuracy,sensitivity and spatial resolution,is more suitable for quantification of the tracer uptake within lesions compared with SPECT.Currently,¹¹C（Carbon-11）,¹³N（Nitrogen-13）,¹⁵O（Oxygen-15）,¹⁸F（Fluorine-18）and ⁶⁸Ga（Gallium-68）are most frequently employed in PET imaging.⁶⁸Ga could be directly eluted from ⁶⁸Ge/⁶⁸Ga generator,avoiding the onsite cyclotron producing which increased the production cost and extending the scope of application to some extent.And ⁶⁸Ge/⁶⁸Ga generator could be eluted for about one year because of the mother nuclide ⁶⁸Ge have a long half-life period.In addition,⁶⁸Ga³⁺is quite suitable for labelling with various N or O donor polypeptide and other small molecular targeting drugs,filling the gap in the detection and diagnosis of some diseases which are unsuitable with using other PET-radiotracers.By virtue of these ideal properties,the application of ⁶⁸Ga in nuclear medicine for PET imaging has been growing widely.In the last few decades,the production techniques of ⁶⁸Ge-⁶⁸Ga at abroad had reached an advanced level.And currently,the commercial ⁶⁸Ge/⁶⁸Ga generator has been developed for many years.However,⁶⁸Ge/⁶⁸Ga generators used for clinical applications in domestic are totally dependent on the imports to the date.Thus,it is necessary to explore the key techniques on the production,separation and preparation of generator for ⁶⁸Ge/⁶⁸Ga generator by ourselves.In our work,the study on preparation and irradiation of Ga-Ni alloy target,the separation and purification of ⁶⁸Ge and the assembling of generator was investigated.Furthermore,the purity of ⁶⁸Ga elutes was detected.And at the same time,⁶⁸Ga product was applied in radiolabeling with DOTATATE and PSMA-617 to detect its suitability.The main conclusions were detailed in following:（1）The Zn target with the thickness of 15 mg cm^-2 was successfully prepared on Al-substrate using vacuum evaporation.In addition,electro-deposition was selected for the preparation of Ga-Ni alloy target.Firstly,the influence of ion concentration,p H of solution,the distance between anode and cathode,current density on the electro-deposition was carried out systematically,determining the optimum electroplating condition.Second,the electroplating tank with the anode and cathode both rotating was designed and prepared.The Ga-Ni alloy deposit with a large surface area,the shape of rectangular and maximum thickness of 120 mg cm^–2 was successfully obtained.Furthermore,both Ga and Ni were evenly distributed in the Ga-Ni alloy layer and the deposit presented a dense and dendrite-free plating.（2）The double-column separation route containing AG1×8/Chelex 100 and Sephadex?G-25 column was established to separate⁶⁸Ge from irradiated Zn or Ga-Ni target.The static and dynamic adsorption on resins were investigated comprehensively.The influence of many factors on the recovery of Ge⁴⁺and the removal of other metal ions was investigated,determining the appropriate experiment conditions.At the same time,adsorption capacity of AG1×8,Chelex 100 and Sephadex?G-25 resin for Zn²⁺,Cu²⁺,Ge⁴⁺was determined separately.Furthermore,the reusability of three resins was also studied.The above results laid the foundation of ⁶⁸Ge separation.（3）Based on the above results,the auto-system for ⁶⁸Ge separation was designed and prepared.This system included control unit,switching valve,peristaltic pump,chromatographic column and sample bottles…The direction of liquid flow was controlled by operating electric switching valve,which making the dead volume of liquid tube system smaller.In addition,the designed auto-system contained a standby system,ensuring the reliability of whole system for ⁶⁸Ge separation.Finally,about 5m Ci of ⁶⁸Ge was succeeded in obtaining by using this auto separation system.The recovery of ⁶⁸Ge could attain about 70%,and the removal of nuclides impurities could attain more than 99.9%.（4）Sn O₂ used for ⁶⁸Ge-⁶⁸Ga generator assembling was synthesized successfully.Sn O₂ exhibited excellent selectivity for Ge⁴⁺.Furthermore,the penetrable adsorption capability of Sn O₂ for Ge⁴⁺could reach to be 0.30±0.02 mg g^–1,satisfying the demand of the preparation of ⁶⁸Ge/⁶⁸Ga generator.In addition,the 5 m Ci Sn O₂-based ⁶⁸Ge/⁶⁸Ga generator was prepared and ⁶⁸Ga can be recovered exceed 70%.The ⁶⁸Ga products generated from Sn O₂-based generator with high radioactive concentration and purity could fulfill for ⁶⁸Ga stipulated by European Pharmacopeia.Furthermore,the suitability of ⁶⁸Ga for synthesis of radiopharmaceuticals can be proved by labeling tests with DOTATATE and PSMA-617.The results demonstrated that the labelling efficiency could reach to be more than 90%.And the ⁶⁸Ga-labelled complex exhibited excellent stability in fetal bovine serum（FBS）and phosphate buffer saline（PBS）.In summary,the separation of ⁶⁸Ge from irradiated Zn or Ga-Ni alloy target by using double-column chromatographic separation technique was succeeded in establishing.The core technology of assembly of Sn O₂-based ⁶⁸Ge/⁶⁸Ga generator was also mastered.These would provide a foundation for production of ⁶⁸Ge at home,which can be expected to improve the current situation that ⁶⁸Ga depends on import.Our work is a matter of great significance.