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Int J Radiat Oncol Biol Phys. 2019 Mar 8. pii: S0360-3016(19)30315-3. doi: 10.1016/j.ijrobp.2019.03.002. [Epub ahead of print]

DCE-MRI and Quantitative Histology Reveal Enhanced Vessel Maturation but Impaired Perfusion and Increased Hypoxia in Bevacizumab-Treated Cervical Carcinoma.

Author information

1
Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
2
Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. Electronic address: einar.k.rofstad@rr-research.no.

Abstract

PURPOSE:

There was a dual purpose of this study: to investigate (a) whether bevacizumab may change the microvasculature and oxygenation of cervical carcinomas and (b) whether any changes can be detected by dynamic contrast-enhanced (DCE)-MRI.

METHODS AND MATERIALS:

Two patient-derived xenograft models of cervical cancer (BK-12 and HL-16) were included in the study. Immunostained histological preparations from untreated and bevacizumab-treated tumors were analyzed with respect to microvascular density (MVD), vessel pericyte coverage, and tumor hypoxia, using CD31, α-SMA, and pimonidazole as markers, respectively. DCE-MRI was carried out at 7.05 T, and parametric images of Ktrans and ve were derived from the data using the Tofts pharmacokinetic model.

RESULTS:

The tumors of both models showed decreased MVD, increased vessel pericyte coverage, and increased vessel maturation after bevacizumab treatment. Bevacizumab-treated tumors were more hypoxic and had lower Ktrans values than untreated tumors in the BK-12 model, whereas bevacizumab-treated and untreated HL-16 tumors had similar hypoxic fractions and similar Ktrans values. Significant correlations were found between median Ktrans and hypoxic fraction, and the data for untreated and bevacizumab-treated tumors were well fitted by the same curve in both tumor models.

CONCLUSIONS:

Bevacizumab-treated tumors show less abnormal microvessels than untreated tumors, but due to treatment-induced vessel pruning, the overall function of the microvasculature may be impaired after bevacizumab treatment, resulting in increased tumor hypoxia. DCE-MRI has great potential for monitoring bevacizumab-induced changes in tumor hypoxia in cervical carcinoma.

KEYWORDS:

Bevacizumab; Cervical Carcinoma; DCE-MRI; Hypoxia; Vessel Maturation

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