Breast tumors frequently metastasize to bone and disrupt local homeostasis to induce osteolytic bone lesions. Causing severe bone pain and even fracture, this degeneration process greatly reduces the quality of life of patients with bone metastasis. However, our inability to monitor early metastatic disease in bone and assess fracture risk hinders therapeutic decision-making and exacerbate patients’ suffering. In this work, we report a longitudinal study to evaluate cancer-colonized bone alterations in a mouse model system with the goal of early detection of minimal disease. Inspired by its label-free and real-time nature as well as its molecular specificity, we employed spontaneous Raman spectroscopy to quantitatively assess early metastasis-induced biochemical alterations in bone composition. Barely two weeks after intracardiac inoculation of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurement in tumor-bearing bones revealed the presence of statistically significant changes in carbonation, mineralization and crystallinity, when compared to their normal counterparts. Our observations underscore the feasibility of diagnosis of compositional changes in tumor-bearing femur and spine, markedly before morphological manifestations are noted via radiographic diagnosis. Our findings offer a fresh molecular understanding of metastasis-induced alternations in bone with previously inaccessible spatiotemporal granularity, and paves the way for development of a fully non-invasive spectroscopic tool for prediction of pathological fracture risk in breast cancer patients.
Chi Zhang and Ishan Barman, "Early determination of molecular alterations in breast cancer-colonized bone with Raman spectroscopy
(Conference Presentation)," Proc. SPIE 10489, Optical Biopsy XVI: Toward Real-Time Spectroscopic Imaging and Diagnosis, 1048911 (Presented at SPIE BiOS: January 31, 2018; Published: 14 March 2018); https://doi.org/10.1117/12.2289575.5751457702001.
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