Asif Noor, Peter D. Roselt, Emily R. McGowan, Stan Poniger, Michael P. Wheatcroft, Paul S. Donnelly
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In this work, a fully-automated process for production of [<sup>89</sup>Zr]ZrCl<sub>4</sub> is reported and its use for the synthesis of [<sup>89</sup>Zr]ZrDFOSq-bisPhPSMA and [<sup>89</sup>Zr]ZrDFOSq-TATE.</p><h3>Results</h3><p>A simple automated process for the isolation of [<sup>89</sup>Zr]ZrCl<sub>4</sub> by trapping [<sup>89</sup>Zr][Zr(ox)<sub>4</sub>]<sup>4−</sup> on a bicarbonate-activated strong anion exchange cartridge followed by elution with 0.1 M HCl in 1 M NaCl was developed. [<sup>89</sup>Zr]ZrCl<sub>4</sub> was routinely recovered from [<sup>89</sup>Zr][Zr(ox)<sub>4</sub>]<sup>4−</sup> in > 95% yield in mildly acidic solution of 0.1 M HCl in 1 M NaCl using a fully-automated process. The [<sup>89</sup>Zr]ZrCl<sub>4</sub> was neutralized with sodium acetate buffer (0.25 M) removing the requirement for cumbersome manual neutralization with strong base. The mixture of [<sup>89</sup>Zr]ZrCl<sub>4</sub> was used for direct automated radiolabeling reactions to produce [<sup>89</sup>Zr]Zr-DFOSquaramide-bisPhPSMA and [<sup>89</sup>Zr]ZrDFOSquaramide-TATE in 80–90% over all RCY in > 95% RCP.</p><h3>Conclusions</h3><p>This method for the production of [<sup>89</sup>Zr]ZrCl<sub>4</sub> does not require removal of HCl by evaporation making this process relatively fast and efficient. The fully automated procedures for the production of [<sup>89</sup>Zr]ZrCl<sub>4</sub> and its use in radiolabeling are well suited to support the centralized and standardized manufacture of multiple dose preparations of zirconium-89 based radiopharmaceuticals.</p></div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"9 1","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00270-2","citationCount":"0","resultStr":"{\"title\":\"Automated synthesis of [89Zr]ZrCl4, [89Zr]ZrDFOSquaramide-bisPh(PSMA) and [89Zr]ZrDFOSquaramide-TATE\",\"authors\":\"Asif Noor, Peter D. Roselt, Emily R. McGowan, Stan Poniger, Michael P. Wheatcroft, Paul S. 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In this work, a fully-automated process for production of [<sup>89</sup>Zr]ZrCl<sub>4</sub> is reported and its use for the synthesis of [<sup>89</sup>Zr]ZrDFOSq-bisPhPSMA and [<sup>89</sup>Zr]ZrDFOSq-TATE.</p><h3>Results</h3><p>A simple automated process for the isolation of [<sup>89</sup>Zr]ZrCl<sub>4</sub> by trapping [<sup>89</sup>Zr][Zr(ox)<sub>4</sub>]<sup>4−</sup> on a bicarbonate-activated strong anion exchange cartridge followed by elution with 0.1 M HCl in 1 M NaCl was developed. [<sup>89</sup>Zr]ZrCl<sub>4</sub> was routinely recovered from [<sup>89</sup>Zr][Zr(ox)<sub>4</sub>]<sup>4−</sup> in > 95% yield in mildly acidic solution of 0.1 M HCl in 1 M NaCl using a fully-automated process. The [<sup>89</sup>Zr]ZrCl<sub>4</sub> was neutralized with sodium acetate buffer (0.25 M) removing the requirement for cumbersome manual neutralization with strong base. The mixture of [<sup>89</sup>Zr]ZrCl<sub>4</sub> was used for direct automated radiolabeling reactions to produce [<sup>89</sup>Zr]Zr-DFOSquaramide-bisPhPSMA and [<sup>89</sup>Zr]ZrDFOSquaramide-TATE in 80–90% over all RCY in > 95% RCP.</p><h3>Conclusions</h3><p>This method for the production of [<sup>89</sup>Zr]ZrCl<sub>4</sub> does not require removal of HCl by evaporation making this process relatively fast and efficient. The fully automated procedures for the production of [<sup>89</sup>Zr]ZrCl<sub>4</sub> and its use in radiolabeling are well suited to support the centralized and standardized manufacture of multiple dose preparations of zirconium-89 based radiopharmaceuticals.</p></div>\",\"PeriodicalId\":534,\"journal\":{\"name\":\"EJNMMI Radiopharmacy and Chemistry\",\"volume\":\"9 1\",\"pages\":\"\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-05-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ejnmmipharmchem.springeropen.com/counter/pdf/10.1186/s41181-024-00270-2\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Radiopharmacy and Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://link.springer.com/article/10.1186/s41181-024-00270-2\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJNMMI Radiopharmacy and Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/s41181-024-00270-2","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
引用次数: 0
摘要
背景：自动[89Zr]Zr-放射性标记过程有可能简化[89Zr]Zr-标记 PET 成像剂的生产。大多数放射性标记方案使用[89Zr][Zr(ox)4]4-作为起始材料，并在放射性标记后去除草酸盐。在某些情况下，用[89Zr]ZrCl4 作为起始材料进行放射性标记，能在较低的反应温度下获得更好的放射化学产率。在这项工作中，报告了一种生产[89Zr]ZrCl4的全自动流程，并将其用于合成[89Zr]ZrDFOSq-bisPhPSMA和[89Zr]ZrDFOSq-TATE：结果：通过在碳酸氢盐活化的强阴离子交换滤芯上捕集[89Zr][Zr(ox)4]4-，然后用 0.1 M HCl 在 1 M NaCl 中洗脱，开发出了一种分离[89Zr]ZrCl4 的简单自动化流程。在 1 M NaCl 中含 0.1 M HCl 的弱酸性溶液中，采用全自动工艺从[89Zr][Zr(ox)4]4-中例行回收了[89Zr]ZrCl4，回收率大于 95%。[89Zr]ZrCl4用醋酸钠缓冲液（0.25 M）中和，无需再用强碱进行繁琐的人工中和。将[89Zr]ZrCl4 混合物用于直接自动放射性标记反应，可生产出[89Zr]Zr-DFOSquaramide-bisPhPSMA 和[89Zr]ZrDFOSquaramide-TATE，RCY 占全部 RCY 的 80-90%，RCP 占 95%以上：这种生产[89Zr]ZrCl4 的方法不需要通过蒸发去除 HCl，因此相对快速高效。全自动生产[89Zr]ZrCl4 的程序及其在放射性标记中的应用非常适合支持以锆 89 为基础的放射性药物多剂量制剂的集中化和标准化生产。
Automated synthesis of [89Zr]ZrCl4, [89Zr]ZrDFOSquaramide-bisPh(PSMA) and [89Zr]ZrDFOSquaramide-TATE
Background
Automated [89Zr]Zr-radiolabeling processes have the potential to streamline the production of [89Zr]Zr-labelled PET imaging agents. Most radiolabeling protocols use [89Zr][Zr(ox)4]4− as the starting material and oxalate is removed after radiolabeling. In some instances, radiolabeling with [89Zr]ZrCl4 as starting material gives better radiochemical yields at lower reaction temperatures. In this work, a fully-automated process for production of [89Zr]ZrCl4 is reported and its use for the synthesis of [89Zr]ZrDFOSq-bisPhPSMA and [89Zr]ZrDFOSq-TATE.
Results
A simple automated process for the isolation of [89Zr]ZrCl4 by trapping [89Zr][Zr(ox)4]4− on a bicarbonate-activated strong anion exchange cartridge followed by elution with 0.1 M HCl in 1 M NaCl was developed. [89Zr]ZrCl4 was routinely recovered from [89Zr][Zr(ox)4]4− in > 95% yield in mildly acidic solution of 0.1 M HCl in 1 M NaCl using a fully-automated process. The [89Zr]ZrCl4 was neutralized with sodium acetate buffer (0.25 M) removing the requirement for cumbersome manual neutralization with strong base. The mixture of [89Zr]ZrCl4 was used for direct automated radiolabeling reactions to produce [89Zr]Zr-DFOSquaramide-bisPhPSMA and [89Zr]ZrDFOSquaramide-TATE in 80–90% over all RCY in > 95% RCP.
Conclusions
This method for the production of [89Zr]ZrCl4 does not require removal of HCl by evaporation making this process relatively fast and efficient. The fully automated procedures for the production of [89Zr]ZrCl4 and its use in radiolabeling are well suited to support the centralized and standardized manufacture of multiple dose preparations of zirconium-89 based radiopharmaceuticals.
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