Bridging the Gap: Lead Isotopes for Interdisciplinary Research★

doi:10.6023/A25060215

Acta Chimica Sinica ›› 2025, Vol. 83 ›› Issue (12): 1561-1575.DOI: 10.6023/A25060215 Previous Articles Next Articles

Special Issue: “中国青年化学家”合辑

Review

跨界之桥: 铅放射性同位素驱动跨学科研究^★

王润泽^a, 储著银^b, 陈俊艺^c, 徐梦欣^a, 李献华^b, 刘志博^a^,^c^,^d^,^e^,^*

^a 昌平实验室北京 102206
^b 中国科学院地质与地球物理研究所岩石圈演化国家重点实验室岩石圈演化国家重点实验室北京 100029
^c 北京大学化学与分子工程学院北京 100871
^d 北京大学-清华大学生命科学联合中心北京 100871
^e 北京大学肿瘤医院核医学科恶性肿瘤发病机制及转化研究教育部重点实验室恶性肿瘤发病机制及转化研究教育部重点实验室北京 100142

投稿日期:2025-06-12 发布日期:2025-08-18

作者简介:

王润泽, 本科毕业于北京师范大学化学学院, 2024年博士毕业于荷兰代尔夫特理工大学, 博士导师为代尔夫特理工大学核反应堆研究所Antonia Denkova教授和Hubert Wolterbeek教授, 同年加入昌平实验室进行博士后研究, 合作导师为刘志博教授. 研究方向为新型放射性核素制备, 靶向核药物研发.

储著银, 中国科学院地质与地球物理研究所研究员. 1992本科毕业于安徽大学化学系, 1995年于中国科学技术大学获应用化学硕士学位, 1998年博士毕业于中国科学院地质研究所. 1998年至今一直任职于中国科学院地质与地球物理研究所, 研究方向为同位素地球化学. 主持多项国家自然科学基金项目, 作为技术骨干参与国家重点研发计划项目, 发表EPSL和AC等Nature Index期刊论文5篇. 曾赴MIT高精度U-Pb地质年代学实验室交流访问.

陈俊艺, 北京大学化学与分子工程学院应用化学系博雅博士后, 本科毕业于南京大学化学化工学院, 2022年博士毕业于北京大学化学与分子工程学院应用化学系, 导师为刘志博教授. 负责北京大学回旋加速器平台与辐照平台的管理运行工作. 研究方向包括放射性药物与核素制备, 核技术应用.

徐梦欣, 现任昌平实验室助理研究员, 2022年博士毕业于北京大学化学与分子工程学院应用化学系, 师从刘志博教授. 2022年到2024年在北京大学从事博士后工作, 2024年加入昌平实验室. 主要研究方向为肿瘤靶向放射性药物的开发与临床转化.

李献华, 中国科学院地质与地球物理研究所研究员, 中国科学院院士. 1983年本科毕业于中国科学技术大学地球化学专业, 1988年在中国科学院地球化学研究所研究生毕业, 获博士学位. 长期从事大陆形成演化和矿产资源同位素年代学和地球化学研究及微区同位素分析新技术方法研发与应用.

刘志博, 北京大学化学与分子工程学院教授, 副院长, 应用化学系主任, 北大-清华生命科学联合中心研究员, 昌平实验室领衔科学家. 获北京市自然科学一等奖(第一完成人)、国家杰出青年基金、新基石基金会科学探索奖、九三学社全国青年科技英才等项目资助或荣誉. 2010年在南京大学获学士学位, 2014年在英属哥伦比亚大学获博士学位, 2014~2016年在美国国立卫生研究院开展博士后研究. 主要从事放射性药物、中子俘获治疗药物和核辐射驱动的物质转化研究.

^★ “中国青年化学家”专辑.

基金资助:
国家自然科学基金(22441051); 国家自然科学基金(22225603); 科技部(2021YFA1601400); 新基石科学基金会(科学探索奖)()

Bridging the Gap: Lead Isotopes for Interdisciplinary Research^★

Runze Wang^a, Zhuyin Chu^b, Junyi Chen^c, Mengxin Xu^a, Xianhua Li^b, Zhibo Liu^a^,^c^,^d^,^e^,^*

^a Changping Laboratory, Beijing 102206
^b State Key Laboratory of Lithospheric Evolution, Institute of Geology and Geophysics, Chinese Academy of Sciences, Beijing 100029
^c College of Chemistry and Molecular Engineering, Peking University, Beijing 100871
^d Peking University-Tsinghua University Center for Life Science, Beijing 100871
^e Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142

Received:2025-06-12 Published:2025-08-18
Contact: * E-mail: zbliu@pku.edu.cn
About author:
^★ For the VSI “Rising Stars in Chemistry”.
Supported by:
National Natural Science Foundation of China(22441051); National Natural Science Foundation of China(22225603); Ministry of Science and Technology of the People's Republic of China(2021YFA1601400); New Cornerstone Science Foundation(The XPLORER PRIZE)()

Radioisotopes of lead have been extensively utilized in interdisciplinary research across nuclear science, healthcare applications, geology, and environmental science since the 20th century, serving as the interdisciplinary bridge connecting different disciplines. Due to the rapid development of nuclear medicine in recent years, the lead-203 and lead-212 radioisotopes have shown significant potential for cancer theranostics, with the ability for accurate diagnosis and effective treatment of tumor. Lead-202 and lead-205 are key components of uranium-lead spikes, which are widely applied in geochronological research on the isotope dilution mass spectrometry (ID-MS) for uranium-lead (U-Pb) dating. As a member from the decay chain of uranium-238, the behavior of lead-210 has been considered as a key mark in sediment dating, atmospheric aerosol transport phenomenon investigation and the monitoring of potential leakage of nuclear fuel from nuclear facilities. However, the production of the above-mentioned lead radioisotopes remains highly challenging, and the current supply is not able to meet the growing demands of these lead radioisotopes across various research fields. In this review, the application of a few selected lead radioisotopes in interdisciplinary research is summarized, with a focus on the production and purification methods for the lead radioisotopes. Finally, insights into prospects for the production and utilization of key radioactive lead isotopes in the future are given.

Key words: lead radioisotopes, radionuclide production, separation and purification, lead, spike

Cite this article

Runze Wang, Zhuyin Chu, Junyi Chen, Mengxin Xu, Xianhua Li, Zhibo Liu. Bridging the Gap: Lead Isotopes for Interdisciplinary Research^★[J]. Acta Chimica Sinica, 2025, 83(12): 1561-1575.

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Fig. & Tab. 24

Figure 1. All the lead isotopes discovered so far, with the half-life or natural abundance

放射性铅同位素	半衰期	衰变模式	应用领域
²⁰²Pb	5.25×10⁴年	EC	地质年代学研究
²⁰³Pb	51.9小时	EC	核医学癌症诊断
²⁰⁵Pb	1.7×10⁷年	EC	地质年代学研究
²¹⁰Pb	22.2年	β^－	环境科学与地球化学研究
²¹²Pb	10.6小时	β^－	核医学癌症治疗

Table 1. Lead radioisotopes mainly discussed in this review

Figure 2. The decay scheme of (a) 212Pb and (b) 203Pb

Figure 3. The production approaches for 212Pb: (a) The decay scheme of 228Th to 212Pb. The daughter radionuclides of 224Ra are not shown; (b) 224Ra/212Pb generator; (c) 228Th/212Pb generator; (d) 228Th/220Rn/212Pb generator; (e) direct separation of 212Pb from natural 232Th

Figure 4. The 224Ra/212Pb generator. (a) The decay scheme of 224Ra; (b) Schematic illustration of a 224Ra/212Pb generator including the elution method; (c) The radioactive equilibrium curve between 224Ra and 212Pb; (d) Elution profile of a 224Ra/212Pb generator over ten days assuming 100% elution efficiency

Figure 5. The separation of 212Pb from 228Th. (a) Schematic illustration of the 228Th/212Pb separation set-up; (b) typical 212Pb elution profile using this set-up; (c) scheme of the improved two-step 228Th/212Pb separation procedure; (d) elution profile of 212Pb using the improved procedure[41-42]

Figure 6. The 220Rn/212Pb gaseous generator[44-45]

Figure 7. Direct extraction of 212Pb from 232Th. (a) The decay scheme of 232Th; (b) absorption of 212Pb from 5 L of 232Th solution on the PB resin; (c) elution profile of 212Pb after being absorbed on the PB resin[48]

Figure 8. Tl targets prepared by electrodeposition for the production of 203Pb in cyclotron. (a) silver target[42]; (b) gold target[52]; (c) copper target[55]; (d) gold target[55]

靶片材料	电镀液组成	参考文献
金片	1 g [^natTl]Tl₂O₃, 0.5 mol/L EDTA, 0.4 mol/L NaOH, 300 µL 20% BRIJ-35, 1.9 mL 35%水合肼, 33.1 mL超纯水	^[52]
金片或铜片	250 mg [^natTl]Tl₂O₃或[²⁰⁵Tl]Tl₂O₃, 300 μL水合肼, 1 g NaOH, 1.5 g EDTA, 10 mL超纯水	^[55]
银片	21 g EDTA, 5 g NaOH, 2.53 mL水合肼, 250 µL BRIJ-35, 90 mL去离子水, 溶解后加入额外2.35 mL 水合肼与250 µL BRIJ-35, 混匀后加至8.475 g [^natTl]Tl₂SO₄或8.949 g of [^natTl]TlNO₃中, 待固体完全溶解后加入额外250 µL水合肼	^[42]

Table 2. Composition of the electroplating buffer for preparing 205Tl targets

Figure 9. The purification procedure of 203Pb as reported by Szuecs et al[56]

Figure 10. The purification procedure of 203Pb as reported by Máthé et al[57]

Figure 11. The purification procedure of 203Pb as reported by Nelson et al[58]

Figure 12. The optimized purification procedure of 203Pb as reported by McNeil et al[42]

Figure 13. The purification procedure of 203Pb as reported by Saini et al[55]

Figure 14. Chemical structure of the precursors of the 203Pb/212Pb radiopharmaceuticals under clinical evaluation. (a) DOTAMTATE[38]; (b) VMT-α-NET[75]; (c) ADVC001[76]; (d) NG001[77]; (e) VMT-01[78]

Figure 15. [68Ga]Ga-DOTATATE PET/CT scan of ten subjects before and after the 4 cycles of [212Pb]Pb-DOTAMTATE treatment. The dose was 2.50 MBq/kg for each cycle[38]

Figure 16. The whole body scan and transversal slice image of [68Ga]Ga-DOTATATE PET/CT (left), 243 MBq [203Pb]Pb-VMT-α-NET (middle) and 86 MBq [212Pb]Pb-VMT-α-NET (right) 2.5 h post injection in the same patient[75]

Figure 17. The first SPECT/CT image of [212Pb]Pb-ADVC001 in human. The image above showed the rapid kidney clearance and low salivary gland uptake of [212Pb]Pb-ADVC001, with 18F-DCFPyl PET/CT scan for comparison. The image below shows the sagittal and coronal images 1.5 h post injection[76]

Figure 18. The decay scheme of (a) 202Pb and (b) 205Pb

核反应	参考文献
¹⁹²Os(¹⁴C,xn)²⁰²Pb	[100]
¹⁹⁸Pt(⁹Be,xn)²⁰²Pb	[101]
²⁰⁴Pb(p,xpyn)²⁰²Pb	[102]
²³⁸UC_x(p,yn)²⁰²Pb	[103]
^natTl(p,xn)^{201/202/203/204/205}Pb	[104]
²⁰³Tl(p,2n)²⁰²Pb	在研

Table 3. Potential nuclear reactions for the production of 202Pb

Figure 19. The production route for 205Pb

Figure 20. The decay scheme of 226Ra

放射性铅同位素	制备设施/方法	核反应/衰变链
²⁰²Pb	回旋加速器	²⁰³Tl(p,2n)²⁰²Pb
²⁰³Pb	回旋加速器	²⁰³Tl(p,n)²⁰³Pb或²⁰⁵Tl(p,3n)²⁰³Pb
²⁰⁵Pb	回旋加速器	²⁰⁶Pb(p,2n)²⁰⁵Bi(EC)²⁰⁵Pb
²¹⁰Pb	²²⁶Ra衰变生成	²²⁶Ra(α)²²²Rn(α)²¹⁸Po(α)²¹⁴Pb(β^-)²¹⁴Bi(β^－)²¹⁴Po(α)²¹⁰Pb
²¹²Pb	核反应堆	²²⁶Ra(n,γ)²²⁷Ra(β^－)²²⁷Ac(n,γ)²²⁸Ac(β^－)²²⁸Th(α)²²⁴Ra(α)²²⁰Rn(α)²¹⁶Po(α)²¹²Pb
	核废料分离	²³²U(α)²²⁸Th(α)²²⁴Ra(α)²²⁰Rn(α)²¹⁶Po(α)²¹²Pb
	天然钍分离	²³²Th(α)²²⁸Ra(β^－)²²⁸Ac(β^－)²²⁸Th(α)²²⁴Ra(α)²²⁰Rn(α)²¹⁶Po(α)²¹²Pb

Table 4. A summary of the sources the lead radioisotopes discussed in this review

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跨界之桥: 铅放射性同位素驱动跨学科研究^★

Bridging the Gap: Lead Isotopes for Interdisciplinary Research^★

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跨界之桥: 铅放射性同位素驱动跨学科研究★

Bridging the Gap: Lead Isotopes for Interdisciplinary Research★

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Fig. & Tab. 24

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跨界之桥: 铅放射性同位素驱动跨学科研究^★

Bridging the Gap: Lead Isotopes for Interdisciplinary Research^★