Chapeau Dylan, Koustoulidou Sofia, Handula Maryana, Beekman Savanne, de Ridder Corrina, Stuurman Debra, de Blois Erik, Buchatskaya Yulia, van der Schilden Karlijn, de Jong Marion, Konijnenberg Mark W, Seimbille Yann
Erasmus MC, Department of Radiology and Nuclear Medicine, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands.
Pharmaceuticals (Basel). 2023 Jul 10;16(7):985. doi: 10.3390/ph16070985.
Peptide receptor radionuclide therapy (PRRT) has been applied to the treatment of neuroendocrine tumors (NETs) for over two decades. However, improvement is still needed, and targeted alpha therapy (TAT) with alpha emitters such as lead-212 (Pb) represents a promising avenue. A series of ligands based on octreotate was developed. Lead-203 was used as an imaging surrogate for the selection of the best candidate for the studies with lead-212. Pb radiolabeling and in vitro assays were carried out, followed by SPECT/CT imaging and ex vivo biodistribution in NCI-H69 tumor-bearing mice. High radiochemical yields (≥99%) and purity (≥96%) were obtained for all ligands. [Pb]Pb-eSOMA-01 and [Pb]Pb-eSOMA-02 showed high stability in PBS and mouse serum up to 24 h, whereas [Pb]Pb-eSOMA-03 was unstable in those conditions. All compounds exhibited a nanomolar affinity (2.5-3.1 nM) for SSTR2. SPECT/CT images revealed high tumor uptake at 1, 4, and 24 h post-injection of [Pb]Pb-eSOMA-01/02. Ex vivo biodistribution studies confirmed that the highest uptake in tumors was observed with [Pb]Pb-eSOMA-01. [Pb]Pb-eESOMA-01 displayed the highest absorbed dose in the tumor (35.49 Gy/MBq) and the lowest absorbed dose in the kidneys (121.73 Gy/MBq) among the three tested radioligands. [Pb]Pb-eSOMA-01 is a promising candidate for targeted alpha therapy of NETs. Further investigations are required to confirm its potential.
肽受体放射性核素治疗（PRRT）已应用于神经内分泌肿瘤（NETs）的治疗二十多年。然而，仍有改进的必要，而使用诸如铅 - 212（Pb）等α发射体的靶向α治疗（TAT）是一条有前景的途径。基于奥曲肽开发了一系列配体。铅 - 203被用作成像替代物，以选择用于铅 - 212研究的最佳候选物。进行了铅放射性标记和体外测定，随后在荷NCI - H69肿瘤小鼠中进行SPECT/CT成像和离体生物分布研究。所有配体均获得了高放射化学产率（≥99%）和纯度（≥96%）。[Pb]Pb - eSOMA - 01和[Pb]Pb - eSOMA - 02在PBS和小鼠血清中直至24小时都表现出高稳定性，而[Pb]Pb - eSOMA - 03在这些条件下不稳定。所有化合物对SSTR2均表现出纳摩尔亲和力（2.5 - 3.1 nM）。SPECT/CT图像显示在注射[Pb]Pb - eSOMA - 01/02后1、4和24小时肿瘤摄取高。离体生物分布研究证实，[Pb]Pb - eSOMA - 01在肿瘤中的摄取最高。在三种测试的放射性配体中，[Pb]Pb - eESOMA - 01在肿瘤中的吸收剂量最高（35.49 Gy/MBq），在肾脏中的吸收剂量最低（121.73 Gy/MBq）。[Pb]Pb - eSOMA - 01是NETs靶向α治疗的一个有前景的候选物。需要进一步研究以确认其潜力。
