Optimized Methods for the Production of High-Purity ²⁰³Pb Using Electroplated Thallium Targets

²⁰³Pb is a surrogate imaging match for ²¹²Pb. This elementally matched pair is emerging as a suitable pair for imaging and targeted radionuclide therapy in cancer care. Because of the half-life (51.9 h) and low-energy γ-rays emitted, ²⁰³Pb is suitable for the development of diagnostic radiopharmaceuticals. The aim of this work was to optimize the production and separation of high-specific-activity ²⁰³Pb using electroplated thallium targets. We further investigated the radiochemistry optimization using a suitable chelator, tetraazacyclododecane-1,4,7-triacetic acid (DO3A), and targeting vector, VMT-α-NET (lead-specific chelator conjugated to tyr3-octreotide via a polyethylene glycol linker). Methods: Targets were prepared by electroplating of natural or enriched (²⁰⁵Tl) thallium metal. Scanning electron microscopy was performed to determine the structure and elemental composition of electroplated targets. Targets were irradiated with 24-MeV protons with varying current and beam time to investigate target durability. ²⁰³Pb was purified from the thallium target material using an extraction resin (lead resin) column followed by a second column using a weak cation-exchange resin to elute the lead isotope as [²⁰³Pb]PbCl₂ Inductively coupled plasma mass spectrometry studies were used to further characterize the separation for trace metal contaminants. Radiolabeling efficiency was also investigated for DO3A chelator and VMT-α-NET (a peptide-based targeting conjugate). Results: Electroplated targets were prepared at a high plating density of 76-114 mg/cm² using a plating time of 5 h. A reproducible separation method was established with a final elution in HCl (400 μL, 1 M) suitable for radiolabeling. Greater than 90% recovery yields were achieved, with an average specific activity of 37.7 ± 5.4 GBq/μmol (1.1 ± 0.1 Ci/μmol). Conclusion: An efficient electroplating method was developed to prepare thallium targets suitable for cyclotron irradiation. A simple and fast separation method was developed for routine ²⁰³Pb production with high recovery yields and purity.