Raman Spectroscopic Signatures Reveal Distinct Biochemical and Temporal Changes in Irradiated Human Breast Adenocarcinoma Xenografts

Abstract

Radiation therapy plays a crucial role in the management of breast cancer. However, current standards of care have yet to accommodate patient-specific radiation sensitivity. Raman spectroscopy is promising for applications in radiobiological studies and as a technique for personalized radiation oncology, since it can detect spectral changes in irradiated tissues. In this study, we used established Raman spectroscopic approaches to investigate the biochemical nature and temporal evolution of spectral changes in human breast adenocarcinoma xenografts after in vivo irradiation. Spectral alterations related to cell cycle variations with radiation dose were identified for tumors treated using a range of single-fraction ionizing radiation doses. Additional dose-dependent spectral changes linked to specific proteins, nucleic acids and lipids were also identified in irradiated tumors with a clear temporal evolution of the expression of these signatures. This study reveals distinct shifts in Raman spectra after in vivo irradiation of human breast adenocarcinoma xenografts, emphasizing the significance of Raman spectroscopy for assessing tumor response during radiation therapy.

Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer

“…Previously, the human breast MDA-MB-231 tumour model was also studied using RS. In this case, RS identified a radiation response signature linked to changes in specific proteins (including tryptophan, proline, phenylalanine and β-sheet amide bands), and no involvement of glycogen related Raman bands was observed [37]. Therefore, to date, the NSCLC H460 tumour model is the only in vivo model for which the radiation-induced glycogen Raman signature has been recovered.…”

“…Mice were treated using a small animal radiation research platform (SARRP, Xstrahl, Gulmay Medical Inc., Suwanee, GA), according to previously described techniques [37]. Briefly, mice were anaesthetized using isoflurane inhalation (2%, in oxygen) and imaged using a single cone beam computed tomography (CBCT) scan.…”

“…These characteristics are favorable for biomedical applications and, in particular, allow for non-targeted monitoring of radiation resistance indicators in cells and tissues. Raman spectroscopy has shown promise as a way to monitor radiation response in a variety of systems including human lens epithelium [30], blood lymphocytes [31], oral [32], cervical [33], breast, prostate and lung cancers [34–37]. In particular, applications of RS to NSCLC have revealed distinct radiation-induced metabolic alterations in cells [35, 38] and tumour xenograft tissue [36].…”

Haralick texture feature analysis for quantifying radiation response heterogeneity in murine models observed using Raman spectroscopic mapping

“…Put another way, glycogen production is heterogeneously distributed throughout the tumour and, furthermore, the extent of heterogeneity exhibits a radiation dose dependence. In a separate study we show that glycogen production is negatively correlated with tumour regression post radiation [30]. Furthermore, the current and past hypoxic state of local tumour morphology is correlated with glycogen production, thus affecting the spatial extent of tumour regression and glycogen production [30].…”

“…In a separate study we show that glycogen production is negatively correlated with tumour regression post radiation [30]. Furthermore, the current and past hypoxic state of local tumour morphology is correlated with glycogen production, thus affecting the spatial extent of tumour regression and glycogen production [30]. While we tackle the radiobiological implications of glycogen production in a separate work [30], it is clear that the Haralick features calculated here are (i) able to quantitate the extent of textural variation as a function of radiation dose, and (ii) correlate well with expected radiobiological trends in our murine models.…”