Early Detection of Metastasis-Hypoxia Temporal Alterations in Orthotopic Breast Cancer Using Photoacoustic and Deuterium Metabolic Imaging: In Vivo Assessments.
- 1The Department of Medical Imaging, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong 510315, P. R. China.
- 2Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong 518055, P. R. China.
Abstract
Breast cancer is the most prevalent malignant tumor in women, with distant metastasis being the leading cause of mortality. Triple-negative breast cancer (TNBC) carries an exceptionally high lung metastasis risk, and once metastatic, the 5-year survival rate is merely ∼10.94%. A critical clinical gap lies in the lack of noninvasive biomarkers for early metastasis prediction, as conventional imaging fails to detect early micrometastasis and dynamic metabolic perturbations. This study aimed to characterize the temporal dynamics of glycolytic flux, lactate metabolism, and hypoxia during breast cancer lung metastasis, and validate metabolic imaging biomarkers for early prediction. Orthotopic TNBC models were established by implanting 4T1 cells into BALB/c mice, followed by longitudinal monitoring using photoacoustic (PA) imaging, deuterium metabolic imaging (DMI), computed tomography (CT), and hematoxylin-eosin staining. A distinct metastatic timeline was identified: lung micrometastases emerged at Week 2, while CT detected macro-metastases only at Week 3. PA imaging revealed the onset of compensatory hypoxia at Week 2 (oxygen saturation decreased from ∼70% to ∼60%). Concurrently, DMI demonstrated a ∼2-fold increase in glucose uptake and >2-fold accumulation of lactate, indicating enhanced aerobic glycolysis. Hypoxia-inducible factor-1α was significantly upregulated at Weeks 2 and 3, coinciding with macro-metastasis progression. The temporal coupling between Week 2 metabolic reprogramming and micrometastasis initiation highlights lactate as a key pro-metastatic metabolite. DMI, combined with PA imaging, enables noninvasive detection of metabolic and hypoxic alterations preceding CT-detectable macro-metastases, providing a predictive biomarker and technical platform for early warning of breast cancer metastasis and precision intervention.
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BibTeX
@article{hang2026early,
title = {{Early Detection of Metastasis-Hypoxia Temporal Alterations in Orthotopic Breast Cancer Using Photoacoustic and Deuterium Metabolic Imaging: In Vivo Assessments.}},
author = {Lifeng Hang and Huijuan Xin and Qian Wan and Ziying Chen and Cuien Zheng and Yuan Xu and Shumei Li and Jin Fang and Laiping Fang and Chao Zou and Guihua Jiang},
journal = {Chemical \& biomedical imaging},
year = {2026},
month = may,
doi = {10.1021/cbmi.6c00060},
url = {https://europepmc.org/article/MED/42953269},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Early Detection of Metastasis-Hypoxia Temporal Alterations in Orthotopic Breast Cancer Using Photoacoustic and Deuterium Metabolic Imaging: In Vivo Assessments.
AU - Lifeng Hang
AU - Huijuan Xin
AU - Qian Wan
AU - Ziying Chen
AU - Cuien Zheng
AU - Yuan Xu
AU - Shumei Li
AU - Jin Fang
AU - Laiping Fang
AU - Chao Zou
AU - Guihua Jiang
PY - 2026
DA - 2026/05/28
JO - Chemical & biomedical imaging
DO - 10.1021/cbmi.6c00060
UR - https://europepmc.org/article/MED/42953269
AB - Breast cancer is the most prevalent malignant tumor in women, with distant metastasis being the leading cause of mortality. Triple-negative breast cancer (TNBC) carries an exceptionally high lung metastasis risk, and once metastatic, the 5-year survival rate is merely ∼10.94%. A critical clinical gap lies in the lack of noninvasive biomarkers for early metastasis prediction, as conventional imaging fails to detect early micrometastasis and dynamic metabolic perturbations. This study aimed to characterize the temporal dynamics of glycolytic flux, lactate metabolism, and hypoxia during breast cancer lung metastasis, and validate metabolic imaging biomarkers for early prediction. Orthotopic TNBC models were established by implanting 4T1 cells into BALB/c mice, followed by longitudinal monitoring using photoacoustic (PA) imaging, deuterium metabolic imaging (DMI), computed tomography (CT), and hematoxylin-eosin staining. A distinct metastatic timeline was identified: lung micrometastases emerged at Week 2, while CT detected macro-metastases only at Week 3. PA imaging revealed the onset of compensatory hypoxia at Week 2 (oxygen saturation decreased from ∼70% to ∼60%). Concurrently, DMI demonstrated a ∼2-fold increase in glucose uptake and >2-fold accumulation of lactate, indicating enhanced aerobic glycolysis. Hypoxia-inducible factor-1α was significantly upregulated at Weeks 2 and 3, coinciding with macro-metastasis progression. The temporal coupling between Week 2 metabolic reprogramming and micrometastasis initiation highlights lactate as a key pro-metastatic metabolite. DMI, combined with PA imaging, enables noninvasive detection of metabolic and hypoxic alterations preceding CT-detectable macro-metastases, providing a predictive biomarker and technical platform for early warning of breast cancer metastasis and precision intervention.
SN - 2832-3637
ER -