Thomas C Wilson, Stephen A Jannetti, Navjot Guru, Nagavarakishore Pillarsetty, Thomas Reiner, Giacomo Pirovano
{"title":"改进螺旋放射治疗剂 123I-MAPi 的放射合成。","authors":"Thomas C Wilson, Stephen A Jannetti, Navjot Guru, Nagavarakishore Pillarsetty, Thomas Reiner, Giacomo Pirovano","doi":"10.1080/09553002.2020.1781283","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong><sup>123</sup>I-MAPi, a novel PARP1-targeted Auger radiotherapeutic has shown promising results in pre-clinical glioma model. Currently, <sup>123</sup>I-MAPi is synthesized using multistep synthesis that results in modest yields and low molar activities (MA) that limits the ability to translate this technology for human studies where high doses are administered. Therefore, new methods are needed to synthesize <sup>123</sup>I-MAPi in high activity yields (AY) and improved MA to facilitate clinical translation and multicenter trials.</p><p><strong>Materials and methods: </strong><sup>123</sup>I-MAPi was prepared in a single step via <sup>123</sup>I-iododetannylation of the corresponding tributylstannane precursor. In vitro internalization assay, subcellular fractionation and confocal microscopy where used to evaluate the performance of <sup>123</sup>I-MAPi in a small cell lung cancer model.</p><p><strong>Results: </strong><sup>123</sup>I-MAPi was synthesized in a single step from the corresponding stannane precursor in AY of 45 ± 2% and MA of 11.8 ± 4.8 GBq <i>µ</i>mol<sup>-1</sup>. In vitro in LX22 cells showed rapid internalization (5 min) with accumulation found predominantly in the membrane, nucleus and chromatin of the cell as determined by subcellular fractionation.</p><p><strong>Conclusions: </strong>Here, we have developed an improved radiosynthesis of <sup>123</sup>I-MAPi, an Auger theranostic agent. This process was achieved using a single step, <sup>123</sup>I-iododestannylation reaction from the corresponding stannane precursor in good AY and MA. <sup>123</sup>I-MAPi was evaluated in vitro in a small cell lung cancer model with high PARP expression, rapid internalization and high nuclear uptake shown.</p>","PeriodicalId":14261,"journal":{"name":"International Journal of Radiation Biology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/09553002.2020.1781283","citationCount":"9","resultStr":"{\"title\":\"Improved radiosynthesis of <sup>123</sup>I-MAPi, an auger theranostic agent.\",\"authors\":\"Thomas C Wilson, Stephen A Jannetti, Navjot Guru, Nagavarakishore Pillarsetty, Thomas Reiner, Giacomo Pirovano\",\"doi\":\"10.1080/09553002.2020.1781283\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong><sup>123</sup>I-MAPi, a novel PARP1-targeted Auger radiotherapeutic has shown promising results in pre-clinical glioma model. Currently, <sup>123</sup>I-MAPi is synthesized using multistep synthesis that results in modest yields and low molar activities (MA) that limits the ability to translate this technology for human studies where high doses are administered. Therefore, new methods are needed to synthesize <sup>123</sup>I-MAPi in high activity yields (AY) and improved MA to facilitate clinical translation and multicenter trials.</p><p><strong>Materials and methods: </strong><sup>123</sup>I-MAPi was prepared in a single step via <sup>123</sup>I-iododetannylation of the corresponding tributylstannane precursor. In vitro internalization assay, subcellular fractionation and confocal microscopy where used to evaluate the performance of <sup>123</sup>I-MAPi in a small cell lung cancer model.</p><p><strong>Results: </strong><sup>123</sup>I-MAPi was synthesized in a single step from the corresponding stannane precursor in AY of 45 ± 2% and MA of 11.8 ± 4.8 GBq <i>µ</i>mol<sup>-1</sup>. In vitro in LX22 cells showed rapid internalization (5 min) with accumulation found predominantly in the membrane, nucleus and chromatin of the cell as determined by subcellular fractionation.</p><p><strong>Conclusions: </strong>Here, we have developed an improved radiosynthesis of <sup>123</sup>I-MAPi, an Auger theranostic agent. This process was achieved using a single step, <sup>123</sup>I-iododestannylation reaction from the corresponding stannane precursor in good AY and MA. <sup>123</sup>I-MAPi was evaluated in vitro in a small cell lung cancer model with high PARP expression, rapid internalization and high nuclear uptake shown.</p>\",\"PeriodicalId\":14261,\"journal\":{\"name\":\"International Journal of Radiation Biology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/09553002.2020.1781283\",\"citationCount\":\"9\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Radiation Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/09553002.2020.1781283\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/7/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Radiation Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/09553002.2020.1781283","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/7/2 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOLOGY","Score":null,"Total":0}
Improved radiosynthesis of 123I-MAPi, an auger theranostic agent.
Purpose: 123I-MAPi, a novel PARP1-targeted Auger radiotherapeutic has shown promising results in pre-clinical glioma model. Currently, 123I-MAPi is synthesized using multistep synthesis that results in modest yields and low molar activities (MA) that limits the ability to translate this technology for human studies where high doses are administered. Therefore, new methods are needed to synthesize 123I-MAPi in high activity yields (AY) and improved MA to facilitate clinical translation and multicenter trials.
Materials and methods: 123I-MAPi was prepared in a single step via 123I-iododetannylation of the corresponding tributylstannane precursor. In vitro internalization assay, subcellular fractionation and confocal microscopy where used to evaluate the performance of 123I-MAPi in a small cell lung cancer model.
Results: 123I-MAPi was synthesized in a single step from the corresponding stannane precursor in AY of 45 ± 2% and MA of 11.8 ± 4.8 GBq µmol-1. In vitro in LX22 cells showed rapid internalization (5 min) with accumulation found predominantly in the membrane, nucleus and chromatin of the cell as determined by subcellular fractionation.
Conclusions: Here, we have developed an improved radiosynthesis of 123I-MAPi, an Auger theranostic agent. This process was achieved using a single step, 123I-iododestannylation reaction from the corresponding stannane precursor in good AY and MA. 123I-MAPi was evaluated in vitro in a small cell lung cancer model with high PARP expression, rapid internalization and high nuclear uptake shown.
期刊介绍:
The International Journal of Radiation Biology publishes original papers, reviews, current topic articles, technical notes/reports, and meeting reports on the effects of ionizing, UV and visible radiation, accelerated particles, electromagnetic fields, ultrasound, heat and related modalities. The focus is on the biological effects of such radiations: from radiation chemistry to the spectrum of responses of living organisms and underlying mechanisms, including genetic abnormalities, repair phenomena, cell death, dose modifying agents and tissue responses. Application of basic studies to medical uses of radiation extends the coverage to practical problems such as physical and chemical adjuvants which improve the effectiveness of radiation in cancer therapy. Assessment of the hazards of low doses of radiation is also considered.