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首页> 外文期刊>EJNMMI Radiopharmacy and Chemistry >Production, purification, and radiolabeling of the 203Pb/212Pb theranostic pair
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Production, purification, and radiolabeling of the 203Pb/212Pb theranostic pair

机译：203pb / 212pb Theranostic对的生产，纯化和放射性标记

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Background Lead-212 ( 212 Pb, t 1/2 ?=?10.6?h) and lead-203 ( 203 Pb, t 1/2 ?=?51.9?h) are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) and single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both 203 Pb and 212 Pb using TRIUMF’s TR13 (13?MeV) and 500?MeV cyclotrons, and subsequently purified and evaluated both radioisotopes using a series of pyridine-modified DOTA analogues in comparison to the commercially available chelates DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TCMC (1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane). Results Proton irradiation (12.8?MeV) of natural and enriched thallium-203 ( 203 Tl) targets gave 203 Pb saturation yields of 134?±?25 and 483?±?3?MBq/μA, respectively. Thorium-228 ( 228 Th, t 1/2 ?=?1.9 y), a by-product of 232 Th proton spallation on TRIUMF’s main 500?MeV beamline (beamline 1A, BL1A), was recovered to build a 228 Th/ 212 Pb generator with the ability to deliver up to 9–10?MBq of 212 Pb daily. Both lead isotopes were purified via solid phase extraction chromatography (Pb resin), and isolated in an acetate form ([ 203/212 Pb]Pb(Oac) 2 ) suitable for direct radiolabeling of chelators and bioconjugates. A series of cyclen-based chelators (herein referred to as DOTA-1Py, -2Py, and -3Py) along with established chelates DOTA and TCMC were evaluated for their ability to complex both 203 Pb and 212 Pb. All chelates incorporated 212 Pb/ 203 Pb efficiently, with higher radiolabeling yields observed for the 212 Pb-complexes. Conclusion The production of 203 Pb and 212 Pb was established using TRIUMF 13?MeV and 500?MeV cyclotrons, respectively. Both production methods provided radiometals suitable for subsequent radiolabeling reactions using known and novel chelates. Furthermore, the novel chelate DOTA-3Py may be a good candidate for biomolecule conjugation and further theranostic 212 Pb/ 203 Pb studies.
机译：背景引线-212（212pb，t 1/2？=Δ10.6？h）和引线-203（203pb，t 1/2？=Δ51.9μl）是元素当量，或匹配的治疗额外放射性同位素对这表明靶向放射性核素治疗（TRT）和单光子发射计算断层摄影（SPECT）的应用巨大潜力。在Triumf，使用Triumf的TR13（13×MEV）和500〜500？MEV环rons，并随后使用一系列吡啶改性的DOTA类似物纯化和评估与市售螯合物DOTA（ 1,4,7,10-四氮杂碳酸二癸烷-1,4,7,10-四乙酸）和TCMC（1,4,7,10-四氮杂-1,4,7,10-四（2-氨基甲酰甲基）环二癸烷） 。结果天然和富集的铊-203（203吨）靶标质子辐射（12.8〜MeV），分别产生了203μm饱和产率为134Ω·α±25和483？±3？MBQ /μA。钍-228（228，T 1/2？=？1.9 y），在Trioum的主要500架子上的232个质子衬里的副产物，回收了Mev Beamline（Beamline 1a，Bl1a），以构建228/212 PB发电机能够提供高达9-10的能力，每日212 PB的MBQ。通过固相萃取色谱（Pb树脂）纯化两种铅同位素，并以乙酸盐形式分离（[203/212Pb] Pb（OAC）2），适用于螯合剂和生物缀合物的直接放射性标记。评价一系列循环基螯合剂（此处称为DOTA-1PY，-200平方米）以及已建立的螯合物和TCMC，以便它们复杂203pb和212 pb。所有螯合物均有效地掺入212pb / 203pb，对于212pb络合物，观察到具有更高的放射性标记产率。结论分别使用TRIUMF 13？MEV和500？MEV环rons建立了203pb和212 pb的生产。两种生产方法都提供了适用于使用已知和新螯合物的后续放射性标记反应的放射性磁性。此外，新型螯合物DOTA-3 PY可以是生物分子缀合的良好候选者，进一步治疗212 PB / 203 PB研究。

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