Anna A. Shchukina , Anastasia D. Zubenko , Oksana V. Tarasenko , Anton A. Larenkov , Viktor B. Bubenshchikov , Ekaterina Y. Chernikova , Yury V. Fedorov , Olga A. Fedorova
{"title":"评估基于吡啶氮冠化合物 H4PATA、PATAM 和 H4PATPA 的螯合剂对 68Ga 和 177Lu 的作用。","authors":"Anna A. Shchukina , Anastasia D. Zubenko , Oksana V. Tarasenko , Anton A. Larenkov , Viktor B. Bubenshchikov , Ekaterina Y. Chernikova , Yury V. Fedorov , Olga A. Fedorova","doi":"10.1016/j.nucmedbio.2024.108972","DOIUrl":null,"url":null,"abstract":"<div><div>In this article, we present the synthesis and characterization of three macrocyclic chelators, <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong>, <strong>PATAM</strong>, and <strong>H</strong><sub><strong>4</strong></sub><strong>PATPA</strong>, based on a pyridine-azacrown compound. Their complexation with <sup>68</sup>Ga and <sup>177</sup>Lu has been thoroughly investigated using MALDI TOF MS, <sup>1</sup>H NMR spectroscopy, radiolabeling studies, and experiments <em>in vitro</em> with fetal bovine serum and a 1000-fold molar excess of <strong>H</strong><sub><strong>4</strong></sub><strong>EDTA</strong>. Our studies have shown that the chelators <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong> and <strong>H</strong><sub><strong>4</strong></sub><strong>PATPA</strong> form complexes at room temperature with both radionuclides (RCY > 80 % and > 90 % for complexes with <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong> and <strong>H</strong><sub><strong>4</strong></sub><strong>PATPA</strong> after 30 min, respectively). The chelator <strong>PATAM</strong> requires high temperature (95 °C) for complexation. <em>In vitro</em> stability assays in fetal bovine serum as well as <strong>H</strong><sub><strong>4</strong></sub><strong>EDTA</strong>-challenge revealed that transchelation occurs for all complexes with <sup>68</sup>Ga. However, complexes of the ligands <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong> and <strong>PATAM</strong> with <sup>177</sup>Lu were found stable. Thus, taking into account the radiolabeling at room temperature and <em>in vitro</em> stability of the complex [<sup>177</sup>Lu]Lu·<strong>PATA</strong>, our investigations revealed the chelator <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong> is a candidate for radiopharmaceutical use with <sup>177</sup>Lu.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"140 ","pages":"Article 108972"},"PeriodicalIF":3.6000,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Evaluation of chelating agents based on pyridine-azacrown compounds H4PATA, PATAM, and H4PATPA for 68Ga and 177Lu\",\"authors\":\"Anna A. Shchukina , Anastasia D. Zubenko , Oksana V. Tarasenko , Anton A. Larenkov , Viktor B. Bubenshchikov , Ekaterina Y. Chernikova , Yury V. Fedorov , Olga A. Fedorova\",\"doi\":\"10.1016/j.nucmedbio.2024.108972\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>In this article, we present the synthesis and characterization of three macrocyclic chelators, <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong>, <strong>PATAM</strong>, and <strong>H</strong><sub><strong>4</strong></sub><strong>PATPA</strong>, based on a pyridine-azacrown compound. Their complexation with <sup>68</sup>Ga and <sup>177</sup>Lu has been thoroughly investigated using MALDI TOF MS, <sup>1</sup>H NMR spectroscopy, radiolabeling studies, and experiments <em>in vitro</em> with fetal bovine serum and a 1000-fold molar excess of <strong>H</strong><sub><strong>4</strong></sub><strong>EDTA</strong>. Our studies have shown that the chelators <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong> and <strong>H</strong><sub><strong>4</strong></sub><strong>PATPA</strong> form complexes at room temperature with both radionuclides (RCY > 80 % and > 90 % for complexes with <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong> and <strong>H</strong><sub><strong>4</strong></sub><strong>PATPA</strong> after 30 min, respectively). The chelator <strong>PATAM</strong> requires high temperature (95 °C) for complexation. <em>In vitro</em> stability assays in fetal bovine serum as well as <strong>H</strong><sub><strong>4</strong></sub><strong>EDTA</strong>-challenge revealed that transchelation occurs for all complexes with <sup>68</sup>Ga. However, complexes of the ligands <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong> and <strong>PATAM</strong> with <sup>177</sup>Lu were found stable. Thus, taking into account the radiolabeling at room temperature and <em>in vitro</em> stability of the complex [<sup>177</sup>Lu]Lu·<strong>PATA</strong>, our investigations revealed the chelator <strong>H</strong><sub><strong>4</strong></sub><strong>PATA</strong> is a candidate for radiopharmaceutical use with <sup>177</sup>Lu.</div></div>\",\"PeriodicalId\":19363,\"journal\":{\"name\":\"Nuclear medicine and biology\",\"volume\":\"140 \",\"pages\":\"Article 108972\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-11-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nuclear medicine and biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0969805124000982\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nuclear medicine and biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969805124000982","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Evaluation of chelating agents based on pyridine-azacrown compounds H4PATA, PATAM, and H4PATPA for 68Ga and 177Lu
In this article, we present the synthesis and characterization of three macrocyclic chelators, H4PATA, PATAM, and H4PATPA, based on a pyridine-azacrown compound. Their complexation with 68Ga and 177Lu has been thoroughly investigated using MALDI TOF MS, 1H NMR spectroscopy, radiolabeling studies, and experiments in vitro with fetal bovine serum and a 1000-fold molar excess of H4EDTA. Our studies have shown that the chelators H4PATA and H4PATPA form complexes at room temperature with both radionuclides (RCY > 80 % and > 90 % for complexes with H4PATA and H4PATPA after 30 min, respectively). The chelator PATAM requires high temperature (95 °C) for complexation. In vitro stability assays in fetal bovine serum as well as H4EDTA-challenge revealed that transchelation occurs for all complexes with 68Ga. However, complexes of the ligands H4PATA and PATAM with 177Lu were found stable. Thus, taking into account the radiolabeling at room temperature and in vitro stability of the complex [177Lu]Lu·PATA, our investigations revealed the chelator H4PATA is a candidate for radiopharmaceutical use with 177Lu.
期刊介绍：
Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized.
These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field.
Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.
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