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

Abstract

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 g-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 radio-chemistry optimization using a suitable chelator, tetraazacyclododecane-1,4,7-triacetic acid (DO3A), and targeting vector, VMT-a-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-a-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 mL, 1 M) suitable for radiolabeling. Greater than 90% recovery yields were achieved, with an average specific activity of 37.7 6 5.4 GBq/mmol (1.1 6 0.1 Ci/mmol). 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.