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Peer-reviewedCC BY 4.0Nuclear Medicine and Biology

Alternative production of Lead-203: Optimizing production, purification, and radiolabelling for enhanced theranostic applications

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Abstract

Introduction this study investigates the production of Lead-203 (203Pb) using a deuteron beam and demonstrates its application with DOTATATE for diagnostic imaging of neuroendocrine tumours (NETs) thanks to its γ-ray emissions well-suited for SPECT imaging. 203Pb presents a high potential in nuclear medicine, as it is the imaging counterpart of part of Lead-212 (212Pb), a radionuclide with an alpha-emitting decay chain used for targeted alpha therapy. Methods Enriched Thallium-205 (205Tl) was electrodeposited onto a gold substrate using a custom-made PEEK cell, with a platinum rod as the auxiliary electrode. The electrodeposition was conducted at a controlled temperature and stirring speed, with reverse pulse potentials applied to obtain a smooth and dense deposit. The 205Tl deposit was then irradiated with deuteron beams at 31 MeV to produce 203Pb. Chemical separation was performed using two columns containing Pb resin. The first column (150 mg resin) was used to remove 205Tl for further recycling and the second column (60 mg resin) was employed to obtain 203Pb in 1 M ammonium acetate at pH 5 ensuring high purity and specific activity. Radiolabelling of DOTATATE with 203Pb was conducted in a modified acetate buffer, and the radiochemical purity and stability were assessed using HPLC and TLC. The stability of [203Pb]Pb-DOTATATE was evaluated over a period of up to 120 h. Results the electrodeposition process, conducted over 8 h, yielded a reproducible 205Tl deposit with an average thickness of 37.7 ± 3.2 μm, which remained stable during irradiation. The chemical separation process achieved a 203Pb purity exceeding 99 % in 1 M ammonium acetate at pH 5, with a specific activity surpassing 3783 TBq/g for an integrated beam current of 175 μAh at calibration time (EOB + 32 h). The radiochemical separation yield during the process was 80.5 %. Radiolabelling of DOTATATE with 203Pb showed a high radiochemical purity (99.1 %) and a stability over 96 h, demonstrating the feasibility of using [203Pb]Pb-DOTATATE for clinical applications. Conclusion Our results support the use of 203Pb produced using deuteron beam as valuable tools in the advancement of personalized nuclear medicine therapies. The high purity and specific activity of 203Pb, achieved through dual Pb resin purification process, along with its effective radiolabelling with DOTATATE at high yield and long stability, underscore its potential for clinical use in diagnostic imaging, especially in neuroendocrine tumours.

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BibTeX
@article{audouin2026alternative,
  title = {{Alternative production of Lead-203: Optimizing production, purification, and radiolabelling for enhanced theranostic applications}},
  author = {Nadia Audouin and Héloïse Dufour and Aurélien Vidal and Nicolas Bozovic and Fabien Brelet and Remy Dureau and Arnaud Guertin and Keerthana Kamalakannan and Etienne Nigron and Tony Prezeau and Maryne Tarinas and Katalin Briand and Lou Galichet and Ferid Haddad and Thomas Sounalet},
  journal = {Nuclear Medicine and Biology},
  year = {2026},
  month = oct,
  doi = {10.1016/j.nucmedbio.2025.109559},
  url = {https://hal.science/hal-05294355v1},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Alternative production of Lead-203: Optimizing production, purification, and radiolabelling for enhanced theranostic applications
AU  - Nadia Audouin
AU  - Héloïse Dufour
AU  - Aurélien Vidal
AU  - Nicolas Bozovic
AU  - Fabien Brelet
AU  - Remy Dureau
AU  - Arnaud Guertin
AU  - Keerthana Kamalakannan
AU  - Etienne Nigron
AU  - Tony Prezeau
AU  - Maryne Tarinas
AU  - Katalin Briand
AU  - Lou Galichet
AU  - Ferid Haddad
AU  - Thomas Sounalet
PY  - 2026
DA  - 2026/10/12
JO  - Nuclear Medicine and Biology
DO  - 10.1016/j.nucmedbio.2025.109559
UR  - https://hal.science/hal-05294355v1
AB  - Introduction this study investigates the production of Lead-203 (203Pb) using a deuteron beam and demonstrates its application with DOTATATE for diagnostic imaging of neuroendocrine tumours (NETs) thanks to its γ-ray emissions well-suited for SPECT imaging. 203Pb presents a high potential in nuclear medicine, as it is the imaging counterpart of part of Lead-212 (212Pb), a radionuclide with an alpha-emitting decay chain used for targeted alpha therapy. Methods Enriched Thallium-205 (205Tl) was electrodeposited onto a gold substrate using a custom-made PEEK cell, with a platinum rod as the auxiliary electrode. The electrodeposition was conducted at a controlled temperature and stirring speed, with reverse pulse potentials applied to obtain a smooth and dense deposit. The 205Tl deposit was then irradiated with deuteron beams at 31 MeV to produce 203Pb. Chemical separation was performed using two columns containing Pb resin. The first column (150 mg resin) was used to remove 205Tl for further recycling and the second column (60 mg resin) was employed to obtain 203Pb in 1 M ammonium acetate at pH 5 ensuring high purity and specific activity. Radiolabelling of DOTATATE with 203Pb was conducted in a modified acetate buffer, and the radiochemical purity and stability were assessed using HPLC and TLC. The stability of [203Pb]Pb-DOTATATE was evaluated over a period of up to 120 h. Results the electrodeposition process, conducted over 8 h, yielded a reproducible 205Tl deposit with an average thickness of 37.7 ± 3.2 μm, which remained stable during irradiation. The chemical separation process achieved a 203Pb purity exceeding 99 % in 1 M ammonium acetate at pH 5, with a specific activity surpassing 3783 TBq/g for an integrated beam current of 175 μAh at calibration time (EOB + 32 h). The radiochemical separation yield during the process was 80.5 %. Radiolabelling of DOTATATE with 203Pb showed a high radiochemical purity (99.1 %) and a stability over 96 h, demonstrating the feasibility of using [203Pb]Pb-DOTATATE for clinical applications. Conclusion Our results support the use of 203Pb produced using deuteron beam as valuable tools in the advancement of personalized nuclear medicine therapies. The high purity and specific activity of 203Pb, achieved through dual Pb resin purification process, along with its effective radiolabelling with DOTATATE at high yield and long stability, underscore its potential for clinical use in diagnostic imaging, especially in neuroendocrine tumours.
SN  - 0969-8051
ER  -