Department of Radiology, University of Alabama at Birmingham, Birmingham, Alabama; and.
Perspective Therapeutics, Inc., Coralville, Iowa.
J Nucl Med. 2023 Nov;64(11):1791-1797. doi: 10.2967/jnumed.123.265976. Epub 2023 Aug 31.
Pb is a surrogate imaging match for Pb. 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, Pb is suitable for the development of diagnostic radiopharmaceuticals. The aim of this work was to optimize the production and separation of high-specific-activity Pb 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). Targets were prepared by electroplating of natural or enriched (Tl) 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. Pb 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 [Pb]PbCl 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). Electroplated targets were prepared at a high plating density of 76-114 mg/cm 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). An efficient electroplating method was developed to prepare thallium targets suitable for cyclotron irradiation. A simple and fast separation method was developed for routine Pb production with high recovery yields and purity.
铅是铅的替代成像匹配物。这种元素匹配对正在成为癌症治疗中成像和靶向放射性核素治疗的合适对。由于半衰期（51.9 小时）和发射的低能γ射线，铅适合开发诊断放射性药物。这项工作的目的是使用电镀铊靶优化高比活度铅的生产和分离。我们进一步研究了使用合适的螯合剂、四氮杂环十二烷-1,4,7-三乙酸（DO3A）和靶向载体 VMT-α-NET（通过聚乙二醇接头与 tyr3-奥曲肽偶联的铅特异性螯合剂）进行放射化学优化。靶标通过电镀天然或富集（Tl）铊金属制备。通过扫描电子显微镜确定电镀靶的结构和元素组成。用 24-MeV 质子照射不同电流和束时间的靶标，以研究靶的耐久性。用萃取树脂（铅树脂）柱从铊靶材料中分离纯化铅，然后用弱阳离子交换树脂柱洗脱铅同位素[Pb]PbCl。电感耦合等离子体质谱研究用于进一步表征痕量金属污染物的分离。还研究了 DO3A 螯合剂和 VMT-α-NET（基于肽的靶向缀合物）的放射性标记效率。电镀靶在 5 小时的电镀时间内以 76-114 mg/cm 的高电镀密度制备。建立了一种可重复的分离方法，最终在 HCl（400 μL，1 M）中洗脱，适合放射性标记。实现了超过 90%的回收产率，平均比活度为 37.7±5.4GBq/μmol（1.1±0.1Ci/μmol）。开发了一种有效的电镀方法来制备适合回旋加速器辐照的铊靶。开发了一种简单快速的分离方法，用于常规 Pb 生产，具有高回收率和纯度。
