Research and application progress of labeling chemistry of radioactive metal nuclides with chelating agents

Liya WEI; Jingfei XU; Jiang YU; Wenbin HOU; Yiliang LI

doi:10.11889/j.0253-3219.2025.hjs.48.250225

NUCLEAR TECHNIQUES, Volume. 48, Issue 6, 060006(2025)

Research and application progress of labeling chemistry of radioactive metal nuclides with chelating agents

Liya WEI, Jingfei XU, Jiang YU, Wenbin HOU, and Yiliang LI^*

Institute of Radiation Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Tianjin 300192, China

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Figures & Tables(13)

Fig. 1. Schematic of the composition of radioactive drugs

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Fig. 2. Diagram of radionuclide decay types and their corresponding applications in nuclear medicine

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Fig. 3. Structural diagram of some selected chelating agents

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Table 1. Properties and applications of selected radioactive metal nuclides^[3,12]

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Table 1. Properties and applications of selected radioactive metal nuclides^[3,12]

放射性核素 Radionuclide	离子半径和配位数 Ionic radius (pm) and Coordination number (CN)	半衰期（t_1/2） Half time (t_1/2) / h	主要衰变模式和分支 Main decay mode and branching	衰变粒子的平均能量 Average energy of decay particle / keV	应用 Application
诊断性核素Diagnostic nuclide
⁶⁸Ga	62 pm (CN=6)	1.13	β⁺ (89%)	β⁺, 830; γ, 511	PET
¹¹¹In	92 pm (CN=8)	67.2	EC (100%)	γ, 171, 245	SPECT
⁶⁴Cu	73 pm (CN=6)	12.7	β⁺ (19%)	656	PET
⁴⁴Sc	87 pm (CN=8)	4.04	β⁺ (94%)	632	PET
⁸⁹Zr	84 pm (CN=8)	78.41	β⁺ (23%)	395.5	PET
²⁰³Pb	119 pm (CN=6)	51.87	γ (81%)	279.2	SPECT
治疗性核素Therapeutic nuclide
¹⁷⁷Lu	98 pm (CN=8)	159	β^- (100%)	134	β^- therapy
⁹⁰Y	102 pm (CN=8)	64	β^- (100%)	934	β^- therapy
⁶⁷Cu	73 pm (CN=6)	61.8	β^- (100%)	561	β^- therapy
²²⁵Ac	112 pm (CN=6)	238	α (100%)	5 800~8 400	α therapy
²¹²Pb	129 pm (CN=8)	10.64	β^- (64%), α (36%)	β^-, 570; α, 6 050	α therapy

Table 2. Labeling parameters and applications of chelating agents for ⁶⁸Ga

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Table 2. Labeling parameters and applications of chelating agents for ⁶⁸Ga

放射性核素 Radionuclide	螯合剂 Chelator	标记条件 Labeling conditions	条件依赖性参数pM	生物共轭物 Bioconjugate	靶点 Target	参考文献 Reference
⁶⁸Ga	DOTA	pH 5.5, 100 ℃, 10 min	18.5	Tyr³-octreotate	SSTR	[8,18]
	NOTA	pH 3, RT, 10 min	26.4	Cys⁴⁰-Leu¹⁴-Exendin 4	GLP-1R	[19,21]
	HBED	pH 4.5, 85 ℃, 3 min	30.8	PSMA-11	PSMA	[22]
	H₂dedpa	pH 4.5, RT, 10 min	27.4	c(RGDyK)	Integrin α_vβ₃	[26]

Table 3. Labeling parameters and applications of chelating agents for ¹⁷⁷Lu

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Table 3. Labeling parameters and applications of chelating agents for ¹⁷⁷Lu

放射性核素 Radionuclide	螯合剂 Chelator	标记条件 Labeling conditions	条件依赖性参数 pM	生物共轭物 Bioconjugate	靶点 Target	参考文献 Reference
¹⁷⁷Lu	DOTA	pH 5.5, 100 °C, 10 min	20.8	Tyr3-octreotate	SSTR	[8]
	H₄octapa	pH 5.5, RT, 15 min	19.8	Trastuzumab	HER2	[36]
	H₄pypa	pH 7, RT, 15 min	22.6	PSMA-617	PSMA	[36]
	bispidine-L26	pH 4.8, RT, 5 min	10.8	PEG2-TATE	SSTR	[40]

Table 4. Labeling parameters and applications of chelating agents for ⁹⁰Y

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Table 4. Labeling parameters and applications of chelating agents for ⁹⁰Y

放射性核素

Radionuclide

螯合剂

Chelator

标记条件

Labeling conditions

条件依赖性参数pM

生物共轭物

Bioconjugate

靶点

Target

参考文献

Reference

⁹⁰Y

DOTA

pH 5.5, 100 ℃, 10 min

19.8

TATE

SSTR

[43]

CHX-A"-DTPA

pH 5.5, RT, 30 min

Trastuzumab

HER2

[44]

H₄octapa

pH 5.5, RT, 15 min

18.1

Trastuzumab

HER2

[42]

Table 5. Labeling parameters and applications of chelating agents for ¹¹¹In

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Table 5. Labeling parameters and applications of chelating agents for ¹¹¹In

放射性核素 Radionuclide	螯合剂 Chelator	标记条件 Labeling conditions	条件依赖性参数pM	生物共轭物 Bioconjugate	靶点 Target	参考文献 Reference
¹¹¹In	DOTA	pH 5.5, 80 ℃, 20 min	18.8	Phe¹-octreotide	SSTR	[47]
	CHX-A"-DTPA	pH 5.5, 40℃, 40 min	24.4~25.7	Phe¹-octreotide	SSTR	[47]
	p-SCN-Bn-H₆phospa	pH 5.5, RT, 30 min	38.64	Trastuzumab	HER2	[48]
	H₄pypa	pH 6, RT, 10 min	30.5	PSMA-617	PSMA	[38,52]
	H₄picoopa	pH 5.5-7.0, RT, 10 min	31.2	Pip-Nle-CycMSH_hex	MC1R	[48]

Table 6. Labeling parameters and applications of chelating agents for ^64/67Cu

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Table 6. Labeling parameters and applications of chelating agents for ^64/67Cu

放射性核素 Radionuclide	螯合剂 Chelator	标记条件 Labeling conditions	条件依赖性参数pM	生物共轭物 Bioconjugate	靶点 Target	参考文献 Reference
^64/67Cu	DOTA	pH 5-6, 90 °C, 30 min	17.6	Dipep	PSMA	[57]
	NOTA	pH 4.5, RT, 10 min	18.2	Dipep	PSMA	[57]
	p-SCN-PhPr-NE3TA	pH 5-7, RT, 10 min	ND	PEG₄-LLP2A	VLA-4	[61]
	TE2A	pH 8, RT, 10 min	ND	Trastuzumab	HER2	[62]

Table 7. Labeling parameters and applications of chelating agents for ⁴⁴Sc

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Table 7. Labeling parameters and applications of chelating agents for ⁴⁴Sc

放射性核素

Radionuclide

螯合剂

Chelator

标记条件

Labeling conditions

条件依赖性参数pM

生物共轭物

Bioconjugate

靶点

Target

参考文献

Reference

⁴⁴Sc

DOTA

pH 2~5, 95 °C,10~30 min

26.5

Tyr³-octreotate

SSTR

[67-68]

AAZTA

pH 2~7, 25 ℃, 30 min

24.72

c(RGDyK)

integrin α_vβ₃

[66]

Table 8. Labeling parameters and applications of chelating agents for ²²⁵Ac

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Table 8. Labeling parameters and applications of chelating agents for ²²⁵Ac

放射性核素 Radionuclide	螯合剂 Chelator	标记条件 Labeling conditions	条件依赖性参数pM	生物共轭物 Bioconjugate	靶点 Target	参考文献 Reference
²²⁵Ac	DOTA	pH 9, 37~60 ℃, 30~120 min	19.2	Trastuzumab	HER2	[67,69]
	H₂macropa	pH 6, RT, 5 min	ND	Codrituzumab	Glypican-3	[70]
	H₂BZmacropa-NCS	pH 6, RT, 5 min	ND	Codrituzumab	Glypican-3	[70]
	H₄py4pa	pH 7, RT, 30 min	ND	Trastuzumab	HER2	[71]
	H₄picoopa	pH 5.5~7.0, RT, 10 min	ND	Pip-Nle-CycMSH_hex	MC1R	[52]

Table 9. Labeling parameters and applications of chelating agents for ⁸⁹Zr

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Table 9. Labeling parameters and applications of chelating agents for ⁸⁹Zr

放射性核素 Radionuclide	螯合剂 Chelator	标记条件 Labeling conditions	条件依赖性参数pM	生物共轭物 Bioconjugate	靶点 Target	参考文献 Reference
⁸⁹Zr	DOTAGA	pH 6.9~7.2, 90 ℃, 45 min	ND	Trastuzumab	HER2	[82]
	DFO	pH 7~7.3, 25 ℃, 60 min	ND	Trastuzumab	HER2	[73]
	DFO*	pH 7.4, RT, 15~30 min	ND	Trastuzumab	HER2	[74]
	DFOcyclo*	pH 7.4, RT, 15~30 min	ND	Trastuzumab	HER2	[75]
	HOPO	pH 7, RT, 10 min	ND	Trastuzumab	HER2	[78]
	FSC	pH 6.8~7.2, 25 °C, 90 min	ND	RDG	HER2	[79]

Table 10. Labeling parameters and applications of chelating agents for ^203/212Pb

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Table 10. Labeling parameters and applications of chelating agents for ^203/212Pb

放射性核素

Radionuclide

螯合剂

Chelator

标记条件

Labeling conditions

条件依赖性参数pM

生物共轭物

Bioconjugate

靶点

Target

参考文献

Reference

^203/212Pb

DOTA

pH 5.5, 75 ℃, 30~60 min

18.7

Phe¹ -Tyr³ -octreotide

SSTR

[87]

DOTAMA

pH 5.4, 85°C, 30 min

Phe¹ -Tyr³ -octreotide

SSTR

[87]

TCMC

pH 4.5, 37°C, 60 min

Trastuzumab

HER2

[85]

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Liya WEI, Jingfei XU, Jiang YU, Wenbin HOU, Yiliang LI. Research and application progress of labeling chemistry of radioactive metal nuclides with chelating agents[J]. NUCLEAR TECHNIQUES, 2025, 48(6): 060006

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Paper Information

Category: Special Topics of Academic Papers at The 27th Annual Meeting of the China Association for Science and Technology

Received: May. 29, 2025

Accepted: --

Published Online: Jul. 25, 2025

The Author Email: Yiliang LI (李祎亮)

DOI:10.11889/j.0253-3219.2025.hjs.48.250225

Topics

laser devices and laser physics

Lasers and Laser Optics

Laser physics

laser manufacturing

Instrumentation, Measurement and Metrology

Table 1. Properties and applications of selected radioactive metal nuclides[3,12]

Table 1. Properties and applications of selected radioactive metal nuclides[3,12]

Table 2. Labeling parameters and applications of chelating agents for 68Ga

Table 2. Labeling parameters and applications of chelating agents for 68Ga

Table 3. Labeling parameters and applications of chelating agents for 177Lu

Table 3. Labeling parameters and applications of chelating agents for 177Lu

Table 4. Labeling parameters and applications of chelating agents for 90Y

Table 4. Labeling parameters and applications of chelating agents for 90Y

Table 5. Labeling parameters and applications of chelating agents for 111In

Table 5. Labeling parameters and applications of chelating agents for 111In

Table 6. Labeling parameters and applications of chelating agents for 64/67Cu

Table 6. Labeling parameters and applications of chelating agents for 64/67Cu

Table 7. Labeling parameters and applications of chelating agents for 44Sc

Table 7. Labeling parameters and applications of chelating agents for 44Sc

Table 8. Labeling parameters and applications of chelating agents for 225Ac

Table 8. Labeling parameters and applications of chelating agents for 225Ac

Table 9. Labeling parameters and applications of chelating agents for 89Zr

Table 9. Labeling parameters and applications of chelating agents for 89Zr

Table 10. Labeling parameters and applications of chelating agents for 203/212Pb

Table 10. Labeling parameters and applications of chelating agents for 203/212Pb

Table 1. Properties and applications of selected radioactive metal nuclides^[3,12]

Table 1. Properties and applications of selected radioactive metal nuclides^[3,12]

Table 2. Labeling parameters and applications of chelating agents for ⁶⁸Ga

Table 2. Labeling parameters and applications of chelating agents for ⁶⁸Ga

Table 3. Labeling parameters and applications of chelating agents for ¹⁷⁷Lu

Table 3. Labeling parameters and applications of chelating agents for ¹⁷⁷Lu

Table 4. Labeling parameters and applications of chelating agents for ⁹⁰Y

Table 4. Labeling parameters and applications of chelating agents for ⁹⁰Y

Table 5. Labeling parameters and applications of chelating agents for ¹¹¹In

Table 5. Labeling parameters and applications of chelating agents for ¹¹¹In

Table 6. Labeling parameters and applications of chelating agents for ^64/67Cu

Table 6. Labeling parameters and applications of chelating agents for ^64/67Cu

Table 7. Labeling parameters and applications of chelating agents for ⁴⁴Sc

Table 7. Labeling parameters and applications of chelating agents for ⁴⁴Sc

Table 8. Labeling parameters and applications of chelating agents for ²²⁵Ac

Table 8. Labeling parameters and applications of chelating agents for ²²⁵Ac

Table 9. Labeling parameters and applications of chelating agents for ⁸⁹Zr

Table 9. Labeling parameters and applications of chelating agents for ⁸⁹Zr

Table 10. Labeling parameters and applications of chelating agents for ^203/212Pb

Table 10. Labeling parameters and applications of chelating agents for ^203/212Pb