Non-invasive visualization of pH changes within the tumor-micro-environment by positron emission tomography

作者：Jürgen Brück, Dominik Schauenburg, S. Kuan, S. Göttert, Benedikt Klasen, Veronika Frommberger, Kazem Ebadi Jalal, Nabil Boui, Aaron Kwiatkowski, Lisa Schake, Tobias Bopp, Tozka Bohn, Tanja Weil, Mathias Schreckenberger, Matthias Miederer · 发表于：EJNMMI Research · 年份：2026 · DOI：10.1186/s13550-026-01383-2 · 研究领域：Medicine

Background Acidic pH values of the tumor microenvironment (TME) have crucial effects on metastatic behavior, host defense, immune regulation and cellular metabolism. Several studies have shown that the acidity of the interstitial space in the TME influences the functions of cancer and stromal cells, particularly regarding immune effects. Changing intratumoral pH might therefore be a potential target for therapy, and pH imaging might guide further developments. We describe radiopharmaceutical probes for positron emission tomography (PET) that exploit the concept of pH-dependent intratumoral hydrolysis of glycosylamine bonds of PET-tracers ([18F]FDG-4-methoxybenzylamine ([18F]FDG-4MBA) and [18F]FDG-benzylamine ([18F]FDG-BA)) to release [18F]FDG as functional moiety with the aim to non-invasively image pH changes. Results Nuclear magnetic resonance (NMR) spectroscopy demonstrated hydrolysis at pseudo first order and showed pH dependent hydrolysis time, at which 50% of [19F]FDG-4-methoxybenzylamine ([19F]FDG-4MBA) was cleaved, ranging from 3 h at pH 7.4 over 60 min at pH 6.9 to 45 min at pH 6.5. Hydrolysis of [18F]FDG-4MBA in human serum at pH 7,6 was similar to comparable pH without serum (below 10% FDG release after 2 h). The glycosylamines [18F]FDG-BA and [18F]FDG-4MBA were relatively stable in vitro at pH 8.3 with less than 15% FDG release from [18F]FDG-4MBA and less than 10% FDG release from [18F]FDG-BA within 60 min. Hydrolysis at acidic pH led to [18F]FDG release at pH 6.0...