Chemotherapeutic effects on breast tumor hemodynamics revealed by eigenspectra multispectral optoacoustic tomography (eMSOT)

Theranostics. 2021 Jun 26;11(16):7813-7828. doi: 10.7150/thno.56173. eCollection 2021.

Abstract

Non-invasive monitoring of hemodynamic tumor responses to chemotherapy could provide unique insights into the development of therapeutic resistance and inform therapeutic decision-making in the clinic. Methods: Here, we examined the longitudinal and dynamic effects of the common chemotherapeutic drug Taxotere on breast tumor (KPL-4) blood volume and oxygen saturation using eigenspectra multispectral optoacoustic tomography (eMSOT) imaging over a period of 41 days. Tumor vascular function was assessed by dynamic oxygen-enhanced eMSOT (OE-eMSOT). The obtained in vivo optoacoustic data were thoroughly validated by ex vivo cryoimaging and immunohistochemical staining against markers of vascularity and hypoxia. Results: We provide the first preclinical evidence that prolonged treatment with Taxotere causes a significant drop in mean whole tumor oxygenation. Furthermore, application of OE-eMSOT showed a diminished vascular response in Taxotere-treated tumors and revealed the presence of static blood pools, indicating increased vascular permeability. Conclusion: Our work has important translational implications and supports the feasibility of eMSOT imaging for non-invasive assessment of tumor microenvironmental responses to chemotherapy.

Keywords: Taxotere; breast cancer; chemotherapy; docetaxel; optoacoustic; photoacoustic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Docetaxel / pharmacology
  • Female
  • Hemodynamics / drug effects
  • Hemodynamics / physiology*
  • Humans
  • Hypoxia / metabolism
  • Mice
  • Mice, SCID
  • Oxygen / metabolism
  • Photoacoustic Techniques / methods
  • Tomography / methods
  • Tomography, Optical / methods*
  • Tomography, X-Ray Computed / methods
  • Tumor Microenvironment / physiology

Substances

  • Docetaxel
  • Oxygen