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Impact of the mouse model and molar amount of injected ligand on the tissue distribution profile of PSMA radioligands

体内分布 LNCaP公司 配体(生物化学) 放射性配体 化学 体外 体内 药代动力学 癌症研究 药理学 医学 内科学 生物化学 癌细胞 癌症 受体 生物 生物技术
作者
Viviane J. Tschan,Francesca Borgna,Roger Schibli,Cristina Müller
出处
期刊:European Journal of Nuclear Medicine and Molecular Imaging [Springer Science+Business Media]
卷期号:49 (2): 470-480 被引量:19
标识
DOI:10.1007/s00259-021-05446-5
摘要

Abstract Purpose Various preclinical study designs are described in the literature for the evaluation of PSMA radioligands. In this study, [ 177 Lu]Lu-Ibu-DAB-PSMA, an albumin-binding radioligand, and [ 177 Lu]Lu-PSMA-617 were investigated and compared under variable experimental conditions. Methods In vitro cell uptake studies were performed with PC-3 PIP and LNCaP tumor cells using a range of molar concentrations (0.75–500 nM) of both radioligands. Biodistribution and SPECT/CT imaging studies were carried out with the respective tumor mouse models using 0.05 nmol and 1.0 nmol injected ligand per mouse. Results In both tumor cell lines, the uptake of the radioligands was increased when using low molar concentrations of the respective ligand. The observed saturation effect at high ligand concentrations was more pronounced for LNCaP cells that express PSMA at lower levels than for PC-3 PIP cells. At all investigated timepoints, the in vivo uptake of both radioligands was higher in PC-3 PIP tumors than in LNCaP tumors. A low molar amount of injected ligand increased the PC-3 PIP tumor uptake mainly for [ 177 Lu]Lu-Ibu-DAB-PSMA; however, the molar amount of ligand was relevant for both radioligands when using LNCaP tumors. Renal retention of both radioligands was, however, up to fourfold higher during the first hours after application of a low ligand amount compared to the high ligand amount. Conclusion The results of this preclinical study underline the relevance of the tumor model and applied ligand amount for the characterization of PSMA radioligands. The application of equal preclinical study designs is crucial to allow the comparison of novel radioligands with existing ones and, thus, predict potential advantages of new radioligands in view of a clinical application.
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