Brühlmann Santiago Andrés, Walther Martin, Blei Magdalena Kerstin, Mamat Constantin, Kopka Klaus, Freudenberg Robert, Kreller Martin
Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstraße 400, 01328, Dresden, Germany.
Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden, 01062, Dresden, Germany.
EJNMMI Radiopharm Chem. 2024 Aug 15;9(1):60. doi: 10.1186/s41181-024-00292-w.
In recent years, targeted alpha therapy has gained importance in the clinics, and in particular, the alpha-emitter Ac plays a fundamental role in this clinical development. Nevertheless, depending on the chelating system no real diagnostic alternative has been established which shares similar chemical properties with this alpha-emitting radionuclide. In fact, the race to launch a diagnostic radionuclide to form a matched pair with Ac is still open, and La features attractive radiation properties to claim this place. However, in order to enable its translation into clinical use, upscaling of the production of this PET radionuclide is needed.
A study on optimal irradiation parameters, separation conditions and an exhaustive product characterization was carried out. In this framework, a proton irradiation of 2 h, 60 µA and 18.7 MeV produced La activities of up to 10.7 GBq at end of bombardment. In addition, the performance of four different chromatographic resins were tested and two optimized purification methods presented, taking approximately 20 min with a La recovery efficiencies of over 98%, decay corrected. High radionuclide purity and apparent molar activity was proved, of over 99.5% and 120 GBq/µmol, respectively, at end of purification. Furthermore, quantitative complexation of PSMA-617 and mcp-M-PSMA were obtained with molar activities up to 80 GBq/µmol. In addition, both La-radioconjugates offered high stability in serum, of over (98.5 ± 0.3)% and (99.20 ± 0.08)%, respectively, for up to 24 h. A first dosimetry estimation was also performed and it was calculated that an La application for imaging with between 350 and 750 MBq would only have an effective dose of 2.1-4.4 mSv, which is comparable to that of F and Ga based radiopharmaceuticals.
In this article we present an overarching study on La production, from the radiation parameters optimization to a clinical dose estimation. Lanthanum-133 activities in the GBq range could be produced, formulated as [La]LaCl with high quality regarding radiolabeling and radionuclide purity. We believe that increasing the La availability will further promote the development of radiopharmaceuticals based on macropa or other chelators suitable for Ac.
近年来，靶向α治疗在临床上变得越来越重要，特别是α发射体锕在这一临床发展中发挥着重要作用。然而，取决于螯合系统，尚未建立与这种发射α粒子的放射性核素具有相似化学性质的真正诊断替代物。事实上，推出一种与锕形成匹配对的诊断放射性核素的竞争仍在进行中，镥具有吸引人的辐射特性以占据这一位置。然而，为了使其转化为临床应用，需要扩大这种正电子发射断层显像（PET）放射性核素的生产规模。
开展了一项关于最佳辐照参数、分离条件及详尽产品表征的研究。在此框架下，在轰击结束时，2小时、60微安和18.7兆电子伏的质子辐照产生了高达10.7吉贝可的镥活度。此外，测试了四种不同色谱树脂的性能，并提出了两种优化的纯化方法，耗时约20分钟，镥的衰变校正回收效率超过98%。在纯化结束时，证明了高放射性核素纯度和表观摩尔活度，分别超过99.5%和120吉贝可/微摩尔。此外，获得了PSMA - 617和mcp - M - PSMA的定量络合，摩尔活度高达80吉贝可/微摩尔。此外，两种镥放射性缀合物在血清中均具有高稳定性，分别在长达24小时内超过（98.5±0.3）%和（99.20±0.08）%。还进行了首次剂量学估计，计算得出350至750兆贝可的镥用于成像时有效剂量仅为2.1 - 4.4毫希沃特，这与基于氟和镓的放射性药物相当。
在本文中，我们展示了一项关于镥生产的全面研究，从辐射参数优化到临床剂量估计。可以生产出吉贝可范围内的镥 - 133活度，以高质量的[镥]氯化镥形式用于放射性标记和放射性核素纯度方面。我们相信增加镥的可得性将进一步推动基于大环配体或其他适合锕的螯合剂的放射性药物的发展。
