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Background <p>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> Results <p>The fluorescent dye Alexa Fluor™ 594 after chelator conjugation was successfully labeled with the positron-emitting radionuclide <sup>68</sup>Ga(III) in a <i>no-carrier-added</i> 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&#xa0;°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 &gt; 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> Conclusions <p>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>

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68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月9日

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  • Jona Wilhelm Gerhards,
  • Laura Schäfer,
  • Daniel Kang,
  • Ute Lindauer,
  • Susanne Lütje,
  • Felix Manuel Mottaghy,
  • Tobias Schmidt,
  • Andreas Theodor Josef Vogg

摘要

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.