Belosi Francesca, Cicoria Gianfranco, Lodi Filippo, Malizia Claudio, Fanti Stefano, Boschi Stefano, Marengo Mario
Medical Physics Department, University Hospital S. Orsola-Malpighi, Bologna, Italy.
Curr Radiopharm. 2013 Jun 6;6(2):72-7. doi: 10.2174/1874471011306020002.
68Ga labeled radiopharmaceuticals, like 68Ga-DOATNOC and other similar peptides, are gaining relevance in PET-CT, thanks to relatively easy local generator production, that do not requires an installed cyclotron. However, generator produced 68Ga is typically of suboptimal purity, mainly due to the breakthrough of the parent radionuclide 68Ge. Modern automated synthesis modules adopt both fractionation methods and purification methods in order to get rid of 68Ge breakthrough. Purification methods are mainly based on based on cationic prepurification even if anionic purification has been adopted as well. This work studies the efficacy of cationic prepurification using commercial STRATA-X-C, as well as distribution of the 68Ge contaminant during all steps of the synthesis of labeled peptides. Generator waste, STRATA-X-C purification cartridge, synthesis waste and the final product are quantitatively analyzed by means of high resolution gamma ray spectrometry. Our results show that current method of purification is highly effective; initial 68Ge breakthrough of the order of 1 kBq is decreased by a factor greater than 100, with removal of about 61% of the contaminant 68Ge in the first purification passage; this allow an efficient labeling, since removal of the remaining impurity happens during chelation in the reactor vessel. In conclusion, the synthesis with modular automated system resulted to reliably produce 68Ga-DOTANOC, with limited if any user intervention. 68Ge content in the final formulation results lower than 2x10(-7)%, avoiding unjustified patient irradiation due to radionuclidic impurities and satisfying quality prerequisites for radiopharmaceutical preparations.
68Ga标记的放射性药物，如68Ga-DOATNOC和其他类似肽，由于相对容易通过本地发生器生产，且不需要安装回旋加速器，因此在PET-CT中越来越受到关注。然而，发生器生产的68Ga纯度通常不理想，主要是由于母体放射性核素68Ge的突破。现代自动化合成模块采用分馏方法和纯化方法以消除68Ge的突破。纯化方法主要基于阳离子预纯化，不过也采用了阴离子纯化。这项工作研究了使用商用STRATA-X-C进行阳离子预纯化的效果，以及68Ge污染物在标记肽合成所有步骤中的分布。通过高分辨率伽马射线光谱法对发生器废料、STRATA-X-C纯化柱、合成废料和最终产品进行定量分析。我们的结果表明，当前的纯化方法非常有效；初始约1 kBq的68Ge突破降低了100倍以上，在第一次纯化过程中去除了约61%的68Ge污染物；这使得能够进行高效标记，因为剩余杂质在反应容器中的螯合过程中被去除。总之，使用模块化自动化系统进行合成能够可靠地生产68Ga-DOTANOC，用户干预有限。最终制剂中的68Ge含量低于2×10(-7)%，避免了因放射性核素杂质导致的不合理患者辐射，并满足放射性药物制剂的质量要求。
