Quantitative In Vivo Monitoring of Hypoxia and Vascularization of Patient-Derived Murine Xenografts of Mantle Cell Lymphoma Using Photoacoustic and Ultrasound Imaging

Ultrasound Med Biol. 2021 Apr;47(4):1099-1107. doi: 10.1016/j.ultrasmedbio.2020.12.010. Epub 2021 Jan 15.

Abstract

Tumor oxygenation and vascularization are important parameters that determine the aggressiveness of the tumor and its resistance to cancer therapies. We introduce dual-modality ultrasound and photoacoustic imaging (US-PAI) for the direct, non-invasive real-time in vivo evaluation of oxygenation and vascularization of patient-derived xenografts (PDXs) of B-cell mantle cell lymphomas. The different optical properties of oxyhemoglobin and deoxyhemoglobin make it possible to determine oxygen saturation (sO2) in tissues using PAI. High-frequency color Doppler imaging enables the visualization of blood flow with high resolution. Tumor oxygenation and vascularization were studied in vivo during the growth of three different subcutaneously implanted patient-derived xenograft (PDX) lymphomas (VFN-M1, VFN-M2 and VFN-M5 R1). Similar values of sO2 (sO2 Vital), determined from US-PAI volumetric analysis, were obtained in small and large VFN-M1 tumors ranging from 37.9 ± 2.2 to 40.5 ± 6.0 sO2 Vital (%) and 37.5 ± 4.0 to 35.7 ± 4.6 sO2 Vital (%) for small and large VFN-M2 PDXs. In contrast, the higher sO2 Vital values ranging from 57.1 ± 4.8 to 40.8 ± 5.7 sO2 Vital (%) (small to large) of VFN-M5 R1 tumors corresponds with the higher aggressiveness of that PDX model. The different tumor percentage vascularization (assessed as micro-vessel areas) of VFN-M1, VFN-M2 and VFN-M5 R1 obtained by color Doppler (2.8 ± 0.1%, 3.8 ± 0.8% and 10.3 ± 2.7%) in large-stage tumors clearly corresponds with their diverse growth and aggressiveness. The data obtained by color Doppler were validated by histology. In conclusion, US-PAI rapidly and accurately provided relevant and reproducible information on tissue oxygenation in PDX tumors in real time without the need for a contrast agent.

Keywords: Mantle cell lymphoma; Patient-derived xenograft; Photoacoustic imaging; Tumor hypoxia; Tumor vascularization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Hypoxia
  • Female
  • Hemoglobins / metabolism
  • Humans
  • Lymphoma, Mantle-Cell / diagnostic imaging*
  • Lymphoma, Mantle-Cell / pathology
  • Lymphoma, Mantle-Cell / physiopathology*
  • Mice
  • Microvascular Density
  • Microvessels / diagnostic imaging
  • Multimodal Imaging
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / diagnostic imaging*
  • Oxygen / metabolism*
  • Oxyhemoglobins / metabolism
  • Photoacoustic Techniques*
  • Tumor Burden
  • Ultrasonography, Doppler, Color*

Substances

  • Hemoglobins
  • Oxyhemoglobins
  • deoxyhemoglobin
  • Oxygen