背景:近年来,靶向α治疗在临床上越来越重要,特别是,α-发射器225Ac在这一临床发展中起着基本作用。然而,根据螯合系统,尚未建立与这种α发射放射性核素具有相似化学性质的真正诊断替代方法。事实上,发射诊断放射性核素以与225Ac配对的竞赛仍在进行中,和133La具有吸引人的辐射特性,声称这个地方。然而,为了使其能够转化为临床使用,需要扩大这种PET放射性核素的生产。
结果:关于最佳辐照参数的研究,进行了分离条件和详尽的产品表征。在这个框架中,质子辐照2小时,在轰击结束时,60µA和18.7MeV产生了高达10.7GBq的133La活性。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,大约20分钟,133La的回收效率超过98%,衰减校正。证明了高放射性核素纯度和表观摩尔活性,超过99.5%和120GBq/μmol,分别,在净化结束时。此外,获得PSMA-617和mcp-M-PSMA的定量络合,摩尔活性高达80GBq/µmol。此外,两种133La-放射性共轭物在血清中都具有很高的稳定性,超过(98.5±0.3)%和(99.20±0.08)%,分别,长达24小时。还进行了第一次剂量测定估计,并且计算出用于350至750MBq成像的133La应用仅具有2.1-4.4mSv的有效剂量,这与18F和68Ga基放射性药物相当。
结论:在本文中,我们对133La的生产进行了总体研究,从辐射参数优化到临床剂量估计。可以产生GBq范围内的镧-133活性,配制为[133La]LaCl3,具有高质量的放射性标记和放射性核素纯度。我们认为,提高133La的可用性将进一步促进基于Macropa或其他适用于225Ac的螯合剂的放射性药物的开发。
BACKGROUND: In recent years, targeted alpha therapy has gained importance in the clinics, and in particular, the alpha-emitter 225Ac 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 225Ac is still open, and 133La 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.
RESULTS: 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 133La 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 133La 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 133La-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 133La 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 18F and 68Ga based radiopharmaceuticals.
CONCLUSIONS: In this article we present an overarching
study on 133La production, from the radiation parameters optimization to a clinical dose estimation. Lanthanum-133 activities in the GBq range could be produced, formulated as [133La]LaCl3 with high quality regarding radiolabeling and radionuclide purity. We believe that increasing the 133La availability will further promote the development of radiopharmaceuticals based on macropa or other chelators suitable for 225Ac.