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20 August 2023, Volume 36 Issue 4
Novel Brain Synaptic Density Nuclide Molecular Probe 18F-SynVesT-1 Radiolabeling, Quality Control and Imaging Analysis
HU Zhengquan, XIANG Shijun, TANG Yongxiang, CHEN Dengming, HU Shuo
2023, 36(4):  373-379.  DOI: 10.7538/tws.2023.36.04.0373
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Neural synapses were the fundamental sites of interneuronal connections and the structural basis for information transmission in brain networks, and alterations in synapse density were closely related to a variety of nervous system disorders. Therefore, in vivo visual evaluation and quantitative measurement of synaptic density have broad clinical application prospects in the diagnosis, therapeutic monitoring, and potential mechanism research for neurological and psychiatric diseases. Previous research demonstrated that synaptic vesicle protein 2A (SV2A) located in neurons' presynaptic membrane of the brain gray matter could effectively reflect the synaptic density of the central nervous system, while also being closely related to neuronal excitatory changes, the epileptogenic network formation progress and epilepsy drug resistance. It was envisaged that novel nuclide molecular probes targeting SV2A will be developed and utilized to measure alterations in synaptic density in a variety of neurological and psychiatric disorders. This study intended to perform radioactive labeling and quality control for the first time on a high-specificity targeted synaptic density PET imaging agent, 18F-SynVesT-1. The GE Tracerlab FXFN module was used for agent automated agent synthesis while the physical and chemical properties, stability, specific activity, bacterial endotoxin, and other elements of the product solution were analyzed for agent quality control. And finally, the 18F-SynVesT-1 PET imaging performance verification was verified using animal models of epilepsy. The results of this study showed that the GE TRACERLAB FXFN module could achieve an efficient synthesis of 18F-SynVesT-1 with an uncalibrated yield of (11.4±2.6)%, and the product solution synthesized could meet the standard requirements of injection safety and routine clinical command for invasively disease evaluation. This study indicated that the objective product 18F-SynVesT-1 synthesized had good quality control performance and that 18F-SynVesT-1 PET/CT could be used for brain synaptic change assessment in vivo imaging, density quantitative evaluation, detection, and analysis of epileptogenic abnormalities.
General Methods, Application Development and Related Problems of Radiochemical Purity Analysis
YAO Jingjing, YANG Weifang, FAN Mingxuan, LU Jie
2023, 36(4):  380-388.  DOI: 10.7538/tws.2023.36.04.0380
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In recent years, the development of innovative radiopharmaceuticals has become a “hot spot”. In these development processes, it is crucial for researchers to createa radiochemical purity analysis method which is accurate, fast, and convenient. In this mini-review, the development trend of radiochemical purity analysis technology is summarized. In addition, based on the guidelines included in the ChP 2020, this mini-review also discusses the key issues in the development and validation of radiochemical purity analysis methods, such as specificity, accuracy and precision, linearity, range, and durability.
Preparation and Clinical Translation Study of 99mTc-labeled Prostate-Specific Membrane Antigen Inhibitor HYNIC-P137
DUAN Xiaojiang, LIAO Xuhe, XIAO Di, ZHANG Zhuochen, ZHANG Junbo, FAN Yan, YANG Xing
2023, 36(4):  389-396.  DOI: 10.7538/tws.2023.36.04.0389
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To develop a low bladder accumulation SPECT prostate cancer imaging agent, 99mTc-P137 was prepared on the basis of 68Ga-P137 structure, and the probe was subjected to detailed preclinical evaluation and preliminary clinical translation studies. The labeled precursor HYNIC-P137 was prepared by solid-phase synthesis method, and the labeled precursor 99mTc was labeled with EDDA as co-ligand, and the product 99mTc-P137 was quality controlled. The lipid-water partition coefficient and in vitro stability of 99mTc-P137 were examined, and its uptake and inhibition on PSMA-positive and negative cells were investigated. Biodistribution in normal Kunming mice and SPECT/CT imaging in hormonal mice were performed, and finally, clinical translation studies were performed. The results showed that the precursor HYNIC-P137 could be easily obtained from solid-phase synthesis, and the labeled product 99mTc-P137 had a radiochemical purity close to 100%, good in vitro stability and high hydrophilicity. Normal Kunming mouse biodistribution showed rapid blood clearance of this probe, which was mainly metabolized by the kidney. MicroSPECT/CT of tumor-bearing mice showed that 99mTc-P137 was concentrated mainly in PSMA-positive tumors and renal regions, and both could be significantly inhibited, showing a high degree of intra-specific specificity. Clinical translation showed low accumulation of 99mTc-P137 in the bladder, high intrahepatic radioactivity, and good detection performance for prostate cancer foci in situ and lymph node metastases. It was shown that 99mTc-P137 with high affinity and low bladder accumulation is a novel ODAP-based SPECT prostate cancer imaging probe.
Automated Radiosynthesis and Micro PET/CT Imaging of 18F-FAPI-42
WANG Hua, WANG Meng, HUANG Shun, SUN Penghui, HU Kongzheng, XIANG Xianhong, LIN Weiyuan, ZHI Shengfang, TANG Ganghua, HAN Yanjiang
2023, 36(4):  397-406.  DOI: 10.7538/tws.2023.36.04.0397
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Fibroblast activation protein is highly expressed in most epithelial malignant tumors. FAP inhibitor (FAPI) has been used in the early diagnosis of tumors after radionuclide labeling. Objective to achieve automated synthesis and quality control of PET imaging agent 18F-FAPI-42. This study was based on the Allinone synthesizer and its accompanying blank kit, and 18F-FAPI-42 was prepared through one-pot reaction automation. Then, Positron Emission Tomography/Computed Tomography (PET/CT) dynamic imaging was performed on the U87-MG model mouse bearing glioblastoma to evaluate its value. The automated synthesis time of 18F-FAPI-42 was within 60 minutes, with a yield of (15.8±3.2)% (n=10, without decay correction), radiochemical purity than 95%, and specific activity of 14.52 GBq/μmol. micro PET/CT dynamic imaging showed that 18F-FAPI-42 had clear tumor development, long radiation retention time, high tumor to muscle uptake ratio, and activity time curve showed that it was mainly excreted through the kidney. The Allinone synthesizer can stably and efficiently synthesize 18F-FAPI-42 that meets drug quality control standards, and the resulting product quality meets clinical requirements. This synthesis method can provide reference and guidance for 18F labeling of NOTA modified compounds.
Review and Suggestions for the Preparation and Quality Control of 68Ga-PSMA-11 Injection
YE Jiajun, ZHANG Mingru, WANG Jia, ZHU Zifan, KANG Fei, YANG Weidong, WANG Jing
2023, 36(4):  407-415.  DOI: 10.7538/tws.2023.36.04.0407
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In this study, a standardized preparation process for 68Ga-PSMA-11 injection was developed by optimizing the labeling conditions, and the quality control standards of 68Ga-PSMA-11 injection applicable to our institution were formulated by combining domestic and international pharmacopoeias. Reviewing the preparation and quality control results of a total of 316 batches of 68Ga-PSMA-11 injections from 2020—2022, it was found that all batches were successfully prepared to obtain 68Ga-PSMA-11 injections, and the quality control results were in full compliance with the proposed standards. The labeling rate of 68Ga-PSMA-11 was (85.3±11.4)%, and it was decreased significantly with increasing total elution volume of 68Ge/68Ga generator, while the elution interval time had little effect on the labeling rate. This study is expected to guide nuclear medicine practitioners to standardize the preparation and quality control process of 68Ga-PSMA-11 injection, thus improving the quality and safety of the drug, and providing a reference for related industry standards.
Exploration of the Traceability System in Radiopharmaceuticals
ZHOU Wenyuan, FAN Yang, LIU Teli, CHEN Zhuo, ZHU Hua, YANG Zhi
2023, 36(4):  416-422.  DOI: 10.7538/tws.2023.36.04.0416
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In recent years, the rapid iteration of innovative technology products in the biomedical industry has given rise to the emerging field of radiopharmaceuticals, which brings with it a series of complex and distinct challenges. Although the popularization of drug regulatory science and technology has achieved the standardization of drug regulatory governance system and effectively covered drug regulatory undertakings, there remains a lack of a scientific, effective and systematic regulatory system for the production, utilization and health effect evaluation of radiopharmaceuticals. To address the prominent issues of radiopharmaceutical supervision in China, it is crucial to focus on market conditions, clinical needs, drug technical review, and other pertinent factors as key areas of concern. By conducting systematic research from the perspective of whole-process cycle management, efforts can be made to explore and summarize the traceability mechanism system for the production process of radiopharmaceuticals, and to clarify the key direction, basic framework and management path of supervision. This will facilitate the establishment of a supervision system that is in line with the characteristics of radiopharmaceuticals and adaptable to their development, thereby promoting the industrial advancement of the industry. Moreover, it will guide the domestic radiopharmaceutical field towards achieving scientific and high-quality development, effectively addressing the unmet clinical needs of patients.
Synthesis and Preliminary Evaluation of Peptide Compounds Targeting CA IX
YANG Zixin, WANG Cheng, LI Jie, JIA Lina, ZHANG Lan
2023, 36(4):  423-428.  DOI: 10.7538/tws.2023.36.04.0423
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In order to synthesize a peptide-based carbonic anhydrase IX (CA IX) imaging probe 68Ga-DOTA-CA IX-P1-4-10, the labeling and quality control methods were developed. The effects of reaction pH and concentration of the peptide DOTA-CA IX-P1-4-10 on the labeling yield were studied. The reaction conditions were confirmed as: pH value 4.0 to 5.0 (n=6), peptide DOTA-CA IX-P1-4-10 concentration 15.0 to 40.0 mg/L (n=6), reaction temperature 100 ℃, and reaction time 10 min. The product was clear, colorless liquid, with no visible particles. The pH of the product was 5 to 7 (n=6), the radiochemical purity of 68Ga-DOTA-CA IX-P1-4-10 was >99.0% (n=6), and the specific activity of 68Ga-DOTA-CA IX-P1-4-10 was 1.0-5.0 GBq/μmol (end of synthesis) (n=6). The lipid-water partition coefficient of the probe was -2.07±0.01 (n=6) which indicated 68Ga-DOTA-CA IX-P1-4-10 was favorable hydrophilicity. 68Ga-DOTA-CA IX-P1-4-10 showed good in vitro stability in saline and fetal bovine serum at 37 ℃, and the radiochemical purity was >95.0% after 4 hours. White mice did not have abnormal behaviors in undue toxicity experiments. Preliminary results of the study showed that the probe 68Ga-DOTA-CA IX-P1-4-10 is worthy of further study with a simple labeling method, high radiochemical purity, good in vitro stability and favorable biosecurity.
Establishment of the Protocol of Intramuscular 223RaCl2 Injection and the Corresponding Evaluation on Feasibility and Safety
LI Xiaohong, ZUO Changjing, LI Xiao
2023, 36(4):  429-434.  DOI: 10.7538/tws.2022.youxian.067
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223RaCl2 injection for bone metastasis of prostate cancer has been approved for clinical marketing and achieved good clinical effects. However, there are some defects to be solved in the actual use process. Changing the route of drug administration is an important way to regulate the metabolic distribution of drugs in vivo. In this study, 223RaCl2 injection was administered by intramuscular injection in the right thigh of rats. SPECT/CT scanning was used to dynamically record the differences in targeting efficiency and metabolic clearance between intramuscular protocol and intravenous protocol. The results showed that the drug diffusion of 223RaCl2 injection at the injection site was completed within 12 hours after intramuscular injection, and the proportion of bone deposition obtained by intramuscular injection was significantly higher than that of intravenous injection group, while the systemic clearance rate was faster. After the completion of the 9 days observation period, no skin burns or blood changes directly caused by 223RaCl2 injection were observed, preliminarily manifesting the safety of the protocol. Therefore, under the premise of strict control of drug volume, 223RaCl2 injection can improve the drug efficiency of bone deposition and avoid some side effects by intramuscular injection.
Dissolution of Sodium Iodide [131I] Capsule in Vitro
YU Kunru, WEI Xianli, MA Chao, WU Jie, LI Xingyuan
2023, 36(4):  435-439.  DOI: 10.7538/tws.2023.36.04.0435
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The dissolution of sodium iodine [131I] capsules for therapy was measured by the real-time online detection device of the dissolution of radiopharmaceuticals, and the dissolution curve was compared with the reference preparation. The results show that the in vitro dissolution behavior of self-made capsules are consistent with that of the reference preparation. It has been verified with good specificity of analysis method, good linearity (r>0.999) in the range of 1.9~108.4 μCi/mL of activity concentration, indicating that the method is accurate and reliable in which the recoveries are all in the range of 90%~110%, RSD<5%, with high precision.
Calibration of Tritium Microcalorimeter and Calorimetric Verification of Tritium Samples
OUYANG Huiping, YUAN Xiaoming, HE Changshui, LI Zhuoxi, ZHANG Peixu, YANG Hongguang
2023, 36(4):  440-445.  DOI: 10.7538/tws.2022.youxian.023
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Radioactive isotope decay gives off heat, which is an important basis for calculating the activity of radioactive isotope. In order to measure the heat emitted by tritium decay, the detection limit test, working curve calibration and tritium sample measurement verification of a low detection limit microcalorimeter of μW grade were carried out. The measurement results show that the detection limit of microcalorimeter is 1.28 μW, i.e. 38 mCi tritium. In this paper, the output thermoelectric potential U-input thermal power P of microcalorimeter was calibrated in the range of 165-5063 μW (5-50 Ci tritium), and the calibration relationship obtained is U(μV)=0.141P(μW), corresponding to the relation between tritium activity and output thermoelectric potential A(Ci)=0.213U(μV), and the liner correlation coefficient is greater than 0.999. The standard deviation of repeated measurement of tritium samples was 1.14%, and the deviation from PVT method was 2.45%. In order to ensure the consistency of measurement, the calorimeter used in this paper reduces the fluctuation of measurement environment through water bath and vacuum environment. The calibrated calorimeter can measure the activity of tritium samples without damaging their integrity. Compared with other tritium measurement methods, calorimetry is more suitable for the measurement of solid tritium samples and has great engineering application value.
Measurement of Proton Beam Distribution by Diamond Detector
DING Yuyang, GAO Fei, DONG Luqi, WANG Feifei, LIU Yuntao, CHEN Yizhen, WANG Ziye, WANG Jingqian
2023, 36(4):  446-450.  DOI: 10.7538/tws.2023.36.04.0446
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Proton beam therapy (PBT) can achieve the effect of precision radiotherapy due to its unique Bragg peak. In the process of proton therapy, the peak can be accurately located to the tumor area, which can give the tumor a larger dose of irradiation, reduce the damage to normal tissues and organs, and reduce the occurrence of side effects. Therefore, it is very important to locate the Bragg peak of proton beam in real time in proton therapy. In this paper, a cyclotron is used to generate proton beam, and a diamond detector is used to test the radiation characteristics of proton beam, and the Bragg peak and the beam spot center are measured (0, 35 mm). Thus, accurate Bragg peak value of proton beam was obtained, which guaranteed the accuracy of proton therapy.
Nuclear Performance of a Cylindrical Fission Ionization Chamber
QIU Shunli, GE Mengtuan, XIAO Wei, DONG Jincheng, ZHOU Yulin, SUN Guangzhi, ZENG Le, LIU Haifeng, PEI Yu, CHENG Hui
2023, 36(4):  451-459.  DOI: 10.7538/tws.2023.36.04.0451
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In order to overcome the difficulties of meeting the engineering application requirements of the technical performance indicators of the fission ionization chamber, to explore the feasibility of the development of the longsensitive zone fission ionization chamber in actual application, and to realize the domestic application of the intermediate range detector for the excore nuclear instrumentation system (NIS) in the third-generation nuclear power plant, a cylindrical fission ionization chamber for the nuclear power plant external nuclear measurement system was developed. Based on the thermal neutron fluence standard device, standard γ radiation device and reactor irradiation hole test platform, the identification characteristics, thermal neutron sensitivity, charge per pulse, average electron collection time, high voltage plateau characteristics, repeatability and γ sensitivity of the fission ionization chamber were tested, and the relationship between the detector performance and temperature was tested. The test results show that the thermal neutron sensitivity of the fission ionization chamber can reach 0.53 s-1/nv, the charge per pulse is 1.88×10-13 C, the average electron collection time is 400 ns, the high voltage platform characteristics platform length ≥400 V, platform slope ≤4%/100 V, γ sensitivity 3.30×10-9 A·Gy-1·h, repeatability maximum value 2.4%, all indicators are better than the design requirements. The successful development of the fission ionization chamber lays a solid foundation for the subsequent development of the long-sensitive zone fission ionization chamber.
Experimental Study on Tritium Concentration and Recovery of Hydrogen Isotope Gas with Low Tritium Abundance
WEI Lefu, LU Jianxin, LI Zhuoxi, LIAN Xudong, GUO Wei, YANG Hongguang
2023, 36(4):  460-465.  DOI: 10.7538/tws.2023.36.04.0460
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In order to further reduce the tritium abundance of hydrogen isotope exhaust with low tritium content, realize the recovery of tritium efficiently, and reduce the impact of tritium emission sources on the environment, this paper carried out the research of low-abundance tritium recovery process based on thermal cycle adsorption process. When the separation column packed with palladium deposited on kieselguhr (Pd/K) is at low temperature, hydrogen isotope gas is injected from the front end, and then the column is controlled to perform a heating-cooling cycle. After several cycles, the light component argon is enriched at the inlet of the separation column, and the recombinant tritium concentration is concentrated at the outlet. The research showed that the gas with a tritium abundance of 3.2% entered the experimental system, and after 7 cycles, the tritium abundance at the inlet of the separation column is less than 0.01%. A total of 7.55 mol of low-abundance gas is processed in the experiment, and finally 7.42 mol of the exhaust gas with a tritium abundance of less than 0.05% was extracted, as well as 72.31 mmol of tritium gas with an abundance of 98.68% and 0.048 mol of a medium-abundance gas with an average abundance of 29.68%. The system tritium recovery rate reached 99.54%. Experiments have verified that the thermal cycle adsorption optimization process can further reduce the tritium abundance in the exhaust gas and directly obtain high-abundance tritium gas products, greatly increasing the effective extraction of tritium.
Research Progress in Radioiodine Labeling Methods of Biomolecules
WANG Yang, LI Zheng, LIU Yuxia, ZHANG Lan, LI Qingnuan
2023, 36(4):  466-478.  DOI: 10.7538/tws.2022.youxian.082
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Radiopharmaceuticals derived from targeted molecules labeled with radioiodine have always been the research hotspots in the field of nuclear medicine. Radioiodine labeling also has a clear application demand in pharmacokinetic research. Methods for radioiodine labeling include direct labeling method and indirect labeling method. Direct labeling method has the advantages of rapid reaction, simple operation and high radiochemical yield, but it has the problems of narrow scope of application and deiodination in vivo; and for the indirect method, although radioiodine labeled drugs shows good stability in vivo, it has the problems as complicated process and low radiochemical yield. With the purpose of providing reference for the development of radioiodine labeled drugs and isotope pharmacokinetics study, this paper introduced the research progress, application scope, advantages and disadvantages of radioiodine labeling methods, and prospected the development of radioiodine labeling methods. 
Development of LEU-based Targets for 99Mo Production
SHEN Yijia, WU Yuxuan, LUO Zhifu
2023, 36(4):  479-489.  DOI: 10.7538/tws.2022.youxian.087
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One of the major isotopes used in nuclear medicine is 99mTc. 99mTc for medical purpose is a decay product of 99Mo, which is produced in research reactors from the fission of 235U. Uranium targets are being converted from highly enriched uranium (HEU) to low enriched uranium (LEU) to prevent nuclear proliferation. Advantages and disadvantages of various target designs are investigated and discussed along current disposal methods. In the present paper,some advice was also given for further exploration.
Development and Challenge of Large Container Photon-counting Imaging Technology
ZHANG Huaxia, WU Zhifang
2023, 36(4):  490-497.  DOI: 10.7538/tws.2023.36.04.0490
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The photon-counting detectors with great application potential, have brought technological innovation to radiation imaging fields. With energy resolving capability, photon-counting detectors will help to enhance radiation image quality, lower radiation dose and increase detection effectiveness. Nowadays, low-energy detection fields including medical diagnostics and luggage inspection have seen extensive and in-depth research on photon-counting imaging technologies. For instance, numerous advancements have appeared in energy spectrum CT, breast inspection, PET, etc. There are, however, not many investigations on photon-counting detectors for the detection of medium and high energy (MeV) rays. To meet the demands of detecting signals with medium to high energy and with high saturation count rate, further technical problem must be solved. This paper primarily introduces photon-counting imaging technology in terms of its features, advantages, latest research on X/γ ray imaging systems for medical and security use, and challenges it faced. In addition, its application status and technical difficulties that need to be broken through in large container inspection area are analyzed.