Assessment of tumor response to radiation and vascular targeting therapy in mice using quantitative ultrasound spectroscopy. Issue 8 (31st July 2015)

• Record Type: Journal Article
• Authors: El Kaffas, Ahmed; Sadeghi‐Naini, Ali; Falou, Omar; Tran, William Tyler; Zhou, Stephanie; Hashim, Amr; Fernandes, Jason; Giles, Anoja; Czarnota, Gregory J.
• Is Part Of: Medical physics. Volume 42:Issue 8(2015)Part 1
• Page Start: 4965
• Page End: 4973
• Publication Date: 2015-07-31
• Subjects: backscatter -- biochemistry -- biomedical ultrasonics -- blood vessels -- cellular biophysics -- drugs -- enzymes -- molecular biophysics -- patient monitoring -- radiation protection -- radiation therapy -- tumours -- ultrasonic scattering; Therapeutic applications, including brachytherapy -- Ultrasonography -- Cell processes -- Spectra of biomolecules -- Molecular interactions; membrane‐protein interactions; Diagnosis using ultrasonic, sonic or infrasonic waves -- Radiation therapy -- Therapeutic activity of chemical compounds or medicinal preparations -- Biochemistry; Beer; Spirits; Wine; Vinegar; Microbiology; Enzymology; Mutation or genetic engineering -- Biological material, e.g. blood, urine; Haemocytometers; quantitative ultrasound -- ultrasound spectroscopy -- QUS -- tumor morphology -- 3D high‐frequency ultrasound -- SU11248 -- bFGF -- vascular normalization -- vascular remodeling -- treatment monitoring -- radiation response; Cancer -- Dosimetry -- Radiation treatment -- Ultrasonography -- Intensity modulated radiation therapy -- Tissues -- Radiofrequency spectra -- Image analysis; Medical physics -- Periodicals; Medical physics; Geneeskunde; Natuurkunde; Toepassingen; Biophysics; Periodicals; Periodicals; Electronic journals; 610.153
• DOI: 10.1118/1.4926554
• Languages: English
• ISSNs: 0094-2405

Abstract

Abstract : Purpose: It is now recognized that the tumor vasculature is in part responsible for regulating tumor responses to radiation therapy. However, the extent to which radiation‐based vascular damage contributes to tumor cell death remains unknown. In this work, quantitative ultrasound spectroscopy (QUS) methods were used to investigate the acute responses of tumors to radiation‐based vascular treatments. Methods: Tumor xenografts (MDA‐MB‐231) were treated with single radiation doses of 2 or 8 Gy alone, or in combination with pharmacological agents that modulate vascular radiosensitivity. The midband fit, the slope, and the 0‐MHz intercept QUS parameters were obtained from a linear‐regression fit to the averaged power spectrum of frequency‐dependent ultrasound backscatter and were used to quantify acute tumor responses following treatment administration. Power spectrums were extracted from raw volumetric radio‐frequency ultrasound data obtained before and 24 h following treatment administration. These parameters have previously been correlated to tumor cell death. Staining using in situ end labeling, carbonic anhydrase 9 and cluster of differentiation 31 of tumor sections were used to assess cell death, oxygenation, and vasculature distributions, respectively. Results: Results indicate a significant midband fit QUS parameter increases of 3.2 ± 0.3 dBr and 5.4 ± 0.5 dBr for tumors treated with 2 and 8 Gy radiation combined with the antiangiogenic agent Sunitinib, respectively. In contrast, tumors treated with radiation alone demonstrated a significant midband fit increase of 4.4 ± 0.3 dBr at 8 Gy only. Preadministration of basic fibroblast growth factor, an endothelial radioprotector, acted to minimize tumor response following single large doses of radiation. Immunohistochemical analysis was in general agreement with QUS findings; an R 2 of 0.9 was observed when quantified cell death was correlated with changes in midband fit. Conclusions: Results from QUS analysis presented in this study confirm that acute tumor response is linked to a vascular effect following high doses of radiation therapy. Overall, this is in agreement with previous reports suggesting that acute tumor radiation response is regulated by a vascular‐driven response. Data also suggest that Sunitinib may enhance tumor radiosensitivity through a vascular remodeling process, and that QUS may be sensitive to changes in tissue properties associated with vascular remodeling. Finally, the work also demonstrates the ability of QUS methods to monitor response to radiation‐based vascular strategies.