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| 001 | 309672 | ||
| 005 | 20260206155923.0 | ||
| 024 | 7 | _ | |a 10.1186/s13550-026-01383-2 |2 doi |
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| 037 | _ | _ | |a DKFZ-2026-00294 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Brück, Jürgen |b 0 |
| 245 | _ | _ | |a Non-invasive visualization of pH changes within the tumor-micro-environment by positron emission tomography. |
| 260 | _ | _ | |a Heidelberg |c 2026 |b Springer |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1770389951_2576295 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 500 | _ | _ | |a #DKTKZFB9# / #NCTZFB26# / epub |
| 520 | _ | _ | |a 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.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 of 71% from [18F]FDG-4MBA and 40% from [18F]FDG-BA at 60 min. In vitro uptake into B16F10 or MC38 cells was pH dependent in contrast to FDG uptake. In a preclinical model bearing the two different acidic subcutaneous tumors (B16F10 and MC38), pH differences in the acidic TME were better discriminated with [18F]FDG-4MBA than with [18F]FDG-BA. In vivo neutralization of the acidic extracellular tumor pH prevented pH-dependent cleavage of [18F]FDG-4MBA resulting in decrease of PET signal.The determination of pH differences by glycosylamines radiotracers and PET imaging in acidic TME may serve as a novel marker for various questions such as interaction of pH regulation and response to immunotherapies. Notably, even small pH differences in the acidic TME of different tumors, in the same in vivo model, could be discriminated. |
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| 650 | _ | 7 | |a Glycosylamine |2 Other |
| 650 | _ | 7 | |a Hydrolysis |2 Other |
| 650 | _ | 7 | |a Radiopharmaceutical |2 Other |
| 650 | _ | 7 | |a Tumor-micro-environment |2 Other |
| 650 | _ | 7 | |a Visualization of pH changes |2 Other |
| 700 | 1 | _ | |a Schauenburg, Dominik |b 1 |
| 700 | 1 | _ | |a Kuan, Seah Ling |b 2 |
| 700 | 1 | _ | |a Göttert, Simeon |b 3 |
| 700 | 1 | _ | |a Klasen, Benedikt |b 4 |
| 700 | 1 | _ | |a Frommberger, Veronika |b 5 |
| 700 | 1 | _ | |a Jalal, Kazem Ebadi |b 6 |
| 700 | 1 | _ | |a Boui, Nabil |b 7 |
| 700 | 1 | _ | |a Kwiatkowski, Aaron |b 8 |
| 700 | 1 | _ | |a Schake, Lisa |b 9 |
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| 700 | 1 | _ | |a Bohn, Tozka |0 P:(DE-HGF)0 |b 11 |
| 700 | 1 | _ | |a Weil, Tanja |b 12 |
| 700 | 1 | _ | |a Schreckenberger, Mathias |b 13 |
| 700 | 1 | _ | |a Miederer, Matthias |0 P:(DE-He78)acb57ebf1d4890d47cfd8ebfb21c6bb0 |b 14 |
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