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Resolution of spatial and temporal heterogeneity in bevacizumab-treated breast tumors by eigenspectra multispectral optoacoustic tomography.

Cancer Res. 80, 5291-5304 (2020)
Postprint DOI
Open Access Green
Understanding temporal and spatial hemodynamic heterogeneity as a function of tumor growth or therapy affects the development of novel therapeutic strategies. In this study, we employed eigenspectra multispectral optoacoustic tomography (eMSOT) as a next-generation optoacousticmethod to impart high accuracy in resolving tumor hemodynamics during bevacizumab therapy in two types of breast cancer xenografts (KPL-4 and MDA-MB-468). Patterns of tumor total hemoglobin concentration (THb) and oxygen saturation (sO(2)) were imaged in control and bevacizumab-treated tumors over the course of 58 days (KPL-4) and 16 days (MDA-MB-468), and the evolution of functional vasculature "normalization" was resolved macroscopically. Aninitial sharp drop in tumor sO(2) andTHb content shortly after the initiation of bevacizumab treatment was followed by a recovery in oxygenation levels. Rim-core subregion analysis revealed steep spatial oxygenation gradients in growing tumors that were reduced after bevacizumab treatment. Critically, eMSOT imaging findings were validated directly by histopathologic assessment of hypoxia (pimonidazole) and vascularity (CD31). These data demonstrate how eMSOT brings new abilities for accurate observation of entire tumor responses to challenges at spatial and temporal dimensions not available by other techniques today.Significance: Accurate assessment of hypoxia and vascularization over space and time is critical for understanding tumor development and the role of spatial heterogeneity in tumor aggressiveness, metastasis, and response to treatment.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Contrast-enhanced Ultrasound; Anti-angiogenic Therapy; Vascular Normalization; In-vivo; Antiangiogenic Therapy; Antitumor-activity; Drug Penetration; Cancer; Combination; Oxygenation
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Journal Cancer Research
Quellenangaben Volume: 80, Issue: 23, Pages: 5291-5304 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place Philadelphia, Pa.
Reviewing status Peer reviewed
Grants DFG