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

• Published in: BMC cancer 2019-05, Vol.19 (1), p.474-13, Article 474
• Main Authors: Van Nest, Samantha J, Nicholson, Leah M, Pavey, Nils, Hindi, Mathew N, Brolo, Alexandre G, Jirasek, Andrew, Lum, Julian J
• Format: Article
• Language: English
• Subjects: Animals; Anoxemia; Antigens, Neoplasm - metabolism; Apoptosis; Autophagy; Cancer therapies; Carbonic Anhydrase IX - metabolism; Carbonic anhydrases; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - radiotherapy; Care and treatment; Cell cycle; Cell Hypoxia; Cell Line, Tumor; Deoxyribonucleic acid; DNA; Fluorescent antibody technique; Gene Expression Regulation, Neoplastic - radiation effects; Glycogen; Glycogen - metabolism; Histones - metabolism; Humans; Hypoxia; Immunofluorescence; Ionizing radiation; Laboratories; Lung cancer; Lung Neoplasms - metabolism; Lung Neoplasms - radiotherapy; Medical research; Metabolic pathways; Metabolic response; Metabolism; Mice; Mice, Inbred NOD; Neoplasm Transplantation; Nitroimidazoles - metabolism; Non-small cell lung cancer; Non-small cell lung carcinoma; Oxygenation; Polysaccharides; Radiation (Physics); Radiation Dosage; Radiation exposure; Radiation measurement; Radiation therapy; Radiosensitivity; Radiotherapy; Raman spectroscopy; Recurrence (Disease); Reoxygenation; Small cell lung cancer; Spectroscopy; Spectrum analysis; Spectrum Analysis, Raman; Treatment Outcome; Tumors; Xenografts
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5686-1

Radiation therapy is a standard form of treating non-small cell lung cancer, however, local recurrence is a major issue with this type of treatment. A better understanding of the metabolic response to radiation therapy may provide insight into improved approaches for local tumour control. Cyclic hypoxia is a well-established determinant that influences radiation response, though its impact on other metabolic pathways that control radiosensitivity remains unclear. We used an established Raman spectroscopic (RS) technique in combination with immunofluorescence staining to measure radiation-induced metabolic responses in human non-small cell lung cancer (NSCLC) tumour xenografts. Tumours were established in NOD.CB17-Prkdc /J mice, and were exposed to radiation doses of 15 Gy or left untreated. Tumours were harvested at 2 h, 1, 3 and 10 days post irradiation. We report that xenografted NSCLC tumours demonstrate rapid and stable metabolic changes, following exposure to 15 Gy radiation doses, which can be measured by RS and are dictated by the extent of local tissue oxygenation. In particular, fluctuations in tissue glycogen content were observed as early as 2 h and as late as 10 days post irradiation. Metabolically, this signature was correlated to the extent of tumour regression. Immunofluorescence staining for γ-H2AX, pimonidazole and carbonic anhydrase IX (CAIX) correlated with RS-identified metabolic changes in hypoxia and reoxygenation following radiation exposure. Our results indicate that RS can identify sequential changes in hypoxia and tumour reoxygenation in NSCLC, that play crucial roles in radiosensitivity.