Radiolabelling DOTA-peptides with 68Ga
Radiolabelling DOTA-peptides with 68Ga
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DOI：
10.1007/s00259-004-1702-y
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发表时间：
2005-04-01
影响因子：
9.1
通讯作者：
Krenning, EP
中科院分区：
文献类型：
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作者：
Breeman, WAP;de Jong, M;Krenning, EP
目的.感兴趣的一个新领域是Ga-68标记的DOTA缀合肽用于正电子发射断层扫描（PET）的应用。市售或自制的发电机需要耗时和繁琐的操作。不经进一步纯化以高比活性进行放射性标记是不可能的，而高比活性对于潜在显示药理学副作用的肽是必需的。在这里，我们提出了实际的方面和结果的放射性标记DOTA-肽与TiO 2为基础的市售Ge-68/Ga-68 generator. Methods。反应动力学和参数的影响纳入的放射性核素在最高可实现的比活度进行了研究。由于在处理高β能量发射体Ga-68期间预期手指剂量较高，因此在放射性标记和体内给药期间进行手指剂量测定测量。发生器的分级洗脱显示，在1 ml中回收了80%的放射性。二价和三价离子污染物，竞争纳入的放射性核素低于50 M，从而避免了进一步繁琐和耗时的纯化。在pH 3.5-4下进行放射性标记。在注射过程中，注射器周围的塑料屏蔽（壁厚>= 7 mm）有效地消除了正电子。在大鼠中，（GaCl 3）-Ga-68从血液中清除缓慢，而Ga-68-EDTA通过肾脏快速清除。Ga-68-DOTATOC在生长抑素受体阳性组织中的摄取较高，注射后1和4 h之间无显著差异。用于PET成像的DOTA-肽可以用Ga-68标记，在20分钟内达到1 GBq/nmol的比活性，使得显示潜在药理学副作用的肽能够临床应用。
Purpose. A new field of interest is the application of Ga-68-labelled DOTA-conjugated peptides for positron emission tomography (PET). The commercially available or house-made generators require time-consuming and tedious handling of the eluate. Radiolabelling at high specific activities without further purification is not possible, while high specific activities are necessary for peptides that potentially display pharmacological side-effects. Here we present the practical aspects and the results of radiolabelling DOTA-peptides with a TiO2-based commercially available Ge-68/Ga-68 generator.Methods. Reaction kinetics and parameters influencing the incorporation of the radionuclide at the highest achievable specific activity were investigated. Since high finger doses were anticipated during handling of the high beta-energy emitter Ga-68, finger dosimetric measurements were performed during radiolabelling and in vivo administration.Results. Fractionated elution of the generator revealed that 80% of the radioactivity was recovered in 1 ml. Bi- and trivalent ionic contaminants that compete for the incorporation of the radionuclide were below 50 M; thus further tedious and time-consuming purification was avoided. Radiolabelling was performed at pH 3.5-4. Plastic shielding (>= 7-mm wall thickness) around the syringe during administration effectively eliminated the positrons. In rats (GaCl3)-Ga-68 had slow clearance from blood, while Ga-68-EDTA was rapidly cleared via the kidneys. Uptake of Ga-68-DOTATOC in somatostatin receptor-positive tissues was high, with no significant difference between 1 and 4 h post injection.Conclusion. DOTA-peptides for PET imaging can be labelled with Ga-68 up to specific activities of 1 GBq per nmol within 20 min, enabling the clinical application of peptides that display potential pharmacological side-effects.