这项研究探讨了电感耦合等离子体质谱法（ICP-MS）是否可作为非放射性金属共价物的体外和体内特征化方法，以预测类似放射性药物的性质。在一个“概念证明”研究中，分别将针对前列腺特异性膜抗原（PSMA）的[175Lu]Lu-PSMA-617和[159Tb]Tb-PSMA-617与它们各自的放射标记类似物[177Lu]Lu-PSMA-617（PLUVICTO，诺华）和[161Tb]Tb-PSMA-617进行比较。细胞样品的ICP-MS和传统的γ计数显示（放射性）金属共价物的体外摄取和内化的结果几乎相同（两种技术之间的绝对差异小于6%），无论使用哪种方法。在体内，注射[175Lu]Lu-/[177Lu]Lu-PSMA-617（41±6％ID/g和44±12％IA/g，分别）和[159Tb]Tb-/[161Tb]Tb-PSMA-617（44±5％ID/g和44±5％IA/g，分别），在PSMA阳性PC-3 PIP肿瘤移植体内发现相同的摄取量。此外，还发现在达到受体饱和的器官（如肾脏）中，使用相同比例的（放射性）金属标记和未标记的连接物对两种方法获得相等的数据是至关重要的（注射后1小时，分别为12±2％ID/g和10±1％IA/g）。本研究的数据表明，高灵敏度的ICP-MS可可靠地和预测性地量化用稳定金属同位素标记的化合物在临床前研究中获得的细胞和组织样本。因此，它可以作为检测放射性配基的现有γ计数方法的有效替代品。

This study addresses the question whether inductively coupled plasma mass spectrometry (ICP-MS) can be used as a method for the in vitro and in vivo characterization of non-radioactive metal conjugates to predict the properties of analogous radiopharmaceuticals. In a "proof-of-concept" study, the prostate-specific membrane antigen (PSMA)-targeting [175Lu]Lu-PSMA-617 and [159Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [177Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [161Tb]Tb-PSMA-617. ICP-MS and conventional γ-counting of the cell samples revealed almost identical results (<6% absolute difference between the two technologies) for the in vitro uptake and internalization of the (radio)metal conjugates, irrespective of the employed methodology. In vivo, an equal uptake in PSMA-positive PC-3 PIP tumor xenografts was determined 1 h after the injection of [175Lu]Lu-/[177Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [159Tb]Tb-/[161Tb]Tb-PSMA-617 (44 ± 5% ID/g and 44 ± 5% IA/g, respectively). It was further revealed that it is crucial to use the same ratios of the (radio)metal-labeled and unlabeled ligands for both methodologies to obtain equal data in organs in which receptor saturation was reached such as the kidneys (12 ± 2% ID/g vs 10 ± 1% IA/g, 1 h after injection). The data of this study demonstrate that the use of high-sensitivity ICP-MS allows reliable and predictive quantification of compounds labeled with stable metal isotopes in cell and tissue samples obtained in preclinical studies. It can, hence, be employed as a valid alternative to the state-of-the-art γ-counting methodology to detect radioactive ligands.