studies on cellular binding and stability of Cu-labeled peptide for tumor imaging

Cu標識ペプチドの腫瘍細胞への結合性および生体内での安定性に関するインビトロ研究

須郷 由美; 大島 康宏; 佐々木 一郎; 石岡 典子

Sugo, Yumi; Ohshima, Yasuhiro; Sasaki, Ichiro; Ishioka, Noriko

In the previous study, we have designed and synthesized Cu-DOTA-MARSGL as a novel positron emission tomography (PET) imaging probe for the human epidermal growth factor receptor 2 (HER2) overexpressing tumors. In order to evaluate the usefulness as a PET imaging probe, further studies on the cellular binding and the stability in human or murine plasma were carried out in this work. In the cellular binding assay, it was observed that the radioactivity bound to the cells was dependent on the HER2 expression level. This result suggests the HER2 specificity of Cu-DOTA-MARSGL. It was also confirmed that Cu-DOTA-MARSGL had high stability in saline, while it had low stability in plasma. The degradation product was analyzed by LC/MS using a non-radioactive preparation. The main peak in the chromatogram after incubation in plasma was assigned to Cu-DOTA-MA, which was formed by an endogenous peptidase. To increase the resistance to the peptidase, a modification of the structure is in progress.