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

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.

Keywords: Chemical separation; Electrodeposition; Pb-203; Radiolabelling; Theranostics.