Jona Wilhelm Gerhards, Laura Schäfer, Daniel Kang, Ute Lindauer, Susanne Lütje, Felix Manuel Mottaghy, Tobias Schmidt, Andreas Theodor Josef Vogg
{"title":"68ga放射性标记荧光染料用于蛛网膜下腔出血潜在的无创多模态成像。","authors":"Jona Wilhelm Gerhards, Laura Schäfer, Daniel Kang, Ute Lindauer, Susanne Lütje, Felix Manuel Mottaghy, Tobias Schmidt, Andreas Theodor Josef Vogg","doi":"10.1186/s41181-025-00348-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Aneurysmal subarachnoid hemorrhage (aSAH) is a distinct type of stroke, primarily caused by the rupture of a brain aneurysm. The underlying mechanisms of aSAH remain incompletely understood, prompting ongoing research in this area. Recent investigations into the perivascular system revealed a distribution disturbance of the dye Alexa Fluor™ 594 during measurements. To further investigate this distribution anomaly, it is proposed to label the dye with a radionuclide for biokinetic tracking in rats by means of positron emission tomography for enhanced imaging and analysis.</p><p><strong>Results: </strong>The fluorescent dye Alexa Fluor™ 594 after chelator conjugation was successfully labeled with the positron-emitting radionuclide <sup>68</sup>Ga(III) in a no-carrier-added form. Initially, the NODA-GA-NHS ester was employed to react with the amino group of Alexa Fluor™ 594 1,5-diaminopentane, facilitating subsequent radiolabeling with <sup>68</sup>Ga. The formation of the Alexa Fluor™ 594-chelator conjugate, as well as the radiolabeling, were investigated as a function of reaction time and temperature. For potential animal experiments, it was necessary to increase the reaction temperature from room temperature to 80 °C to optimize the reaction conditions, given the short half-life of <sup>68</sup>Ga. Optimal labeling conditions were established, achieving a radiochemical yield of > 85%. Separation and purification of n.c.a. [<sup>68</sup>Ga]Ga-NODA-GA-Alexa Fluor™ 594 were conducted, with impurities remaining below 3%.</p><p><strong>Conclusions: </strong>This experimental approach successfully yields the desired radiolabeled dye, which is now available for animal studies, potentially offering enhanced insight into the mechanisms of aSAH.</p>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"10 1","pages":"41"},"PeriodicalIF":4.4000,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240878/pdf/","citationCount":"0","resultStr":"{\"title\":\"<sup>68</sup>Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage.\",\"authors\":\"Jona Wilhelm Gerhards, Laura Schäfer, Daniel Kang, Ute Lindauer, Susanne Lütje, Felix Manuel Mottaghy, Tobias Schmidt, Andreas Theodor Josef Vogg\",\"doi\":\"10.1186/s41181-025-00348-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Aneurysmal subarachnoid hemorrhage (aSAH) is a distinct type of stroke, primarily caused by the rupture of a brain aneurysm. The underlying mechanisms of aSAH remain incompletely understood, prompting ongoing research in this area. Recent investigations into the perivascular system revealed a distribution disturbance of the dye Alexa Fluor™ 594 during measurements. To further investigate this distribution anomaly, it is proposed to label the dye with a radionuclide for biokinetic tracking in rats by means of positron emission tomography for enhanced imaging and analysis.</p><p><strong>Results: </strong>The fluorescent dye Alexa Fluor™ 594 after chelator conjugation was successfully labeled with the positron-emitting radionuclide <sup>68</sup>Ga(III) in a no-carrier-added form. Initially, the NODA-GA-NHS ester was employed to react with the amino group of Alexa Fluor™ 594 1,5-diaminopentane, facilitating subsequent radiolabeling with <sup>68</sup>Ga. The formation of the Alexa Fluor™ 594-chelator conjugate, as well as the radiolabeling, were investigated as a function of reaction time and temperature. For potential animal experiments, it was necessary to increase the reaction temperature from room temperature to 80 °C to optimize the reaction conditions, given the short half-life of <sup>68</sup>Ga. Optimal labeling conditions were established, achieving a radiochemical yield of > 85%. Separation and purification of n.c.a. [<sup>68</sup>Ga]Ga-NODA-GA-Alexa Fluor™ 594 were conducted, with impurities remaining below 3%.</p><p><strong>Conclusions: </strong>This experimental approach successfully yields the desired radiolabeled dye, which is now available for animal studies, potentially offering enhanced insight into the mechanisms of aSAH.</p>\",\"PeriodicalId\":534,\"journal\":{\"name\":\"EJNMMI Radiopharmacy and Chemistry\",\"volume\":\"10 1\",\"pages\":\"41\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2025-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240878/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Radiopharmacy and Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s41181-025-00348-5\",\"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://doi.org/10.1186/s41181-025-00348-5","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage.
Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a distinct type of stroke, primarily caused by the rupture of a brain aneurysm. The underlying mechanisms of aSAH remain incompletely understood, prompting ongoing research in this area. Recent investigations into the perivascular system revealed a distribution disturbance of the dye Alexa Fluor™ 594 during measurements. To further investigate this distribution anomaly, it is proposed to label the dye with a radionuclide for biokinetic tracking in rats by means of positron emission tomography for enhanced imaging and analysis.
Results: The fluorescent dye Alexa Fluor™ 594 after chelator conjugation was successfully labeled with the positron-emitting radionuclide 68Ga(III) in a no-carrier-added form. Initially, the NODA-GA-NHS ester was employed to react with the amino group of Alexa Fluor™ 594 1,5-diaminopentane, facilitating subsequent radiolabeling with 68Ga. The formation of the Alexa Fluor™ 594-chelator conjugate, as well as the radiolabeling, were investigated as a function of reaction time and temperature. For potential animal experiments, it was necessary to increase the reaction temperature from room temperature to 80 °C to optimize the reaction conditions, given the short half-life of 68Ga. Optimal labeling conditions were established, achieving a radiochemical yield of > 85%. Separation and purification of n.c.a. [68Ga]Ga-NODA-GA-Alexa Fluor™ 594 were conducted, with impurities remaining below 3%.
Conclusions: This experimental approach successfully yields the desired radiolabeled dye, which is now available for animal studies, potentially offering enhanced insight into the mechanisms of aSAH.