68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage
Abstract 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 syst...
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SpringerOpen
2025-07-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-025-00348-5 |
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| author | Jona Wilhelm Gerhards Laura Schäfer Daniel Kang Ute Lindauer Susanne Lütje Felix Manuel Mottaghy Tobias Schmidt Andreas Theodor Josef Vogg |
| author_facet | Jona Wilhelm Gerhards Laura Schäfer Daniel Kang Ute Lindauer Susanne Lütje Felix Manuel Mottaghy Tobias Schmidt Andreas Theodor Josef Vogg |
| author_sort | Jona Wilhelm Gerhards |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-d0bc026dee87478f80d9fea110e2afc7 |
| institution | DOAJ |
| issn | 2365-421X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | SpringerOpen |
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| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj-art-d0bc026dee87478f80d9fea110e2afc72025-08-20T03:06:36ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2025-07-0110111010.1186/s41181-025-00348-568Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhageJona Wilhelm Gerhards0Laura Schäfer1Daniel Kang2Ute Lindauer3Susanne Lütje4Felix Manuel Mottaghy5Tobias Schmidt6Andreas Theodor Josef Vogg7Department of Nuclear Medicine, RWTH Aachen University HospitalDepartment of Nuclear Medicine, RWTH Aachen University HospitalDepartment of Nuclear Medicine, RWTH Aachen University HospitalTranslational Neurosurgery and Neurobiology, Department of Neurosurgery, RWTH Aachen University HospitalDepartment of Nuclear Medicine, RWTH Aachen University HospitalDepartment of Nuclear Medicine, RWTH Aachen University HospitalTranslational Neurosurgery and Neurobiology, Department of Neurosurgery, RWTH Aachen University HospitalDepartment of Nuclear Medicine, RWTH Aachen University HospitalAbstract 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.https://doi.org/10.1186/s41181-025-00348-5StrokeSubarachnoid hemorrhageGallium-68Alexa Fluor™ 594NODA-GA-NHS esterPositron emission tomography |
| spellingShingle | Jona Wilhelm Gerhards Laura Schäfer Daniel Kang Ute Lindauer Susanne Lütje Felix Manuel Mottaghy Tobias Schmidt Andreas Theodor Josef Vogg 68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage EJNMMI Radiopharmacy and Chemistry Stroke Subarachnoid hemorrhage Gallium-68 Alexa Fluor™ 594 NODA-GA-NHS ester Positron emission tomography |
| title | 68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage |
| title_full | 68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage |
| title_fullStr | 68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage |
| title_full_unstemmed | 68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage |
| title_short | 68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage |
| title_sort | 68ga radiolabeled fluorescent dye for potential non invasive multimodal imaging of subarachnoid hemorrhage |
| topic | Stroke Subarachnoid hemorrhage Gallium-68 Alexa Fluor™ 594 NODA-GA-NHS ester Positron emission tomography |
| url | https://doi.org/10.1186/s41181-025-00348-5 |
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