| Autor: |
Wallimann RH; Novartis Institutes for Biomedical Research, Novartis, 4056 Basel, Switzerland.; Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland., Schindler P; Novartis Institutes for Biomedical Research, Novartis, 4056 Basel, Switzerland., Hensinger H; Novartis Institutes for Biomedical Research, Novartis, 4056 Basel, Switzerland., Tschan VJ; Center for Radiopharmaceutical Sciences, ETH-PSI, Paul Scherrer Institute, 5232 Villigen, Switzerland., Busslinger SD; Center for Radiopharmaceutical Sciences, ETH-PSI, Paul Scherrer Institute, 5232 Villigen, Switzerland., Kneuer R; Novartis Institutes for Biomedical Research, Novartis, 4056 Basel, Switzerland., Müller C; Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.; Center for Radiopharmaceutical Sciences, ETH-PSI, Paul Scherrer Institute, 5232 Villigen, Switzerland., Schibli R; Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.; Center for Radiopharmaceutical Sciences, ETH-PSI, Paul Scherrer Institute, 5232 Villigen, Switzerland. |
| Abstrakt: |
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 [ 175 Lu]Lu-PSMA-617 and [ 159 Tb]Tb-PSMA-617 were compared with their respective radiolabeled analogues, [ 177 Lu]Lu-PSMA-617 (PLUVICTO, Novartis) and [ 161 Tb]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 [ 175 Lu]Lu-/[ 177 Lu]Lu-PSMA-617 (41 ± 6% ID/g and 44 ± 12% IA/g, respectively) and [ 159 Tb]Tb-/[ 161 Tb]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. |
