ArticleBreast cancer research : BCR2025
In vivo imaging of the spatial heterogeneity of intratumoral acidosis (pH) as a marker of the metastatic phenotype in breast cancer.
Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- pH responsive nanoplatforms for radiosensitization and radioprotection in cancer therapy.Discover oncology · 2026Review
- Research progress on precision targeted therapy strategies for breast cancer based on tumor microenvironment.iScience · 2026Review
- Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering.Journal of hematology & oncology · 2026Review
- Multimodal radiomics incorporating intratumoral heterogeneity for prognostic assessment of metastatic outcomes in invasive breast cancer.Breast cancer research : BCR · 2026Article
- Brain Tumor Imaging with Iopamidol CEST MRI: In Vivo Detection and Validation.Chemical & biomedical imaging · 2026Article
- The Role of Tumor pH in Breast Cancer Imaging: Biology, Diagnostic Applications, and Emerging Techniques.Diagnostics (Basel, Switzerland) · 2025Review
- Low-intensity pulsed ultrasound (LIPUS)-augmented calcicoptosis by calcium-based nanoparticles for enhanced immunogenic cell death induction in triple-negative breast cancer.Journal of nanobiotechnology · 2025Article
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Abstract
backgroundMetabolic alterations, including acidosis in the tumor microenvironment, have been extensively linked to more aggressive phenotypes and increased therapy resistance. However, current imaging techniques are limited in their ability to capture extracellular tumor acidosis precisely and assess spatial heterogeneity in vivo, making its association with augmented malignancy poorly understood. In this study, we investigated whether Magnetic Resonance Imaging- Chemical Exchange Saturation Transfer (MRI-CEST) technique for tumor pH imaging of intratumoral acidosis could differentiate between metastatic and non-metastatic breast cancers.
methodsIsogenic metastatic (4T1) and non-metastatic (67NR) breast cancer cell lines were characterized for their metabolic and acidosis features, including LDH-A/PDK-1 expression, glucose consumption, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Potential relationship between tumor acidosis, vascularization and hypoxia with metastatic potential was assessed in vivo by MRI-based imaging approaches in orthotopic breast tumors. Validation of MRI findings was assessed ex vivo by western blot, immunohistochemistry and immunofluorescence assays for a multiparametric characterization of tumor microenvironment and metabolic properties.
resultsWe observed a higher energetic profile of the 4T1 cells compared to the 67NR cells, alongside elevated glycolytic (LDH-A, PDK-1), hypoxia (CAIX, Pimonidazole), and vascularization (CD31) markers in 4T1 orthotopic primary tumors, which were associated with a greater metastatic propensity. MRI-CEST tumor pH imaging revealed increased extracellular tumor acidity in 4T1 tumors, along with marked spatial intratumoral heterogeneity, in contrast to the more homogenous 67NR tumors, as further confirmed by LAMP-2 staining. Notably, this spatial intratumor heterogeneity in acidosis enables clear differentiation between high- and low-malignancy tumors.
conclusionsThese findings underscore the role of tumor acidosis and its spatial heterogeneity in promoting aggressive phenotypes and highlight the potential of in vivo tumor pH imaging as a marker of malignancy in breast cancers.
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