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Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours

  • Magnetic Resonance
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Abstract

Objectives

To evaluate effects of a vascular-disrupting agent on rodent tumour models.

Methods

Twenty rats with liver rhabdomyosarcomas received ZD6126 intravenously at 20 mg/kg, and 10 vehicle-treated rats were used as controls. Multiple sequences, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI) with the microvascular permeability constant (K), were acquired at baseline, 1 h, 24 h and 48 h post-treatment by using 1.5-T MRI. [18F]fluorodeoxyglucose micro-positron emission tomography (18F-FDG µPET) was acquired pre- and post-treatment. The imaging biomarkers including tumour volume, enhancement ratio, necrosis ratio, apparent diffusion coefficient (ADC) and K from MRI, and maximal standardised uptake value (SUVmax) from FDG µPET were quantified and correlated with postmortem microangiography and histopathology.

Results

In the ZD6126-treated group, tumours grew slower with higher necrosis ratio at 48 h (P < 0.05), corresponding well to histopathology; tumour K decreased from 1 h until 24 h, and partially recovered at 48 h (P < 0.05), parallel to the evolving enhancement ratios (P < 0.05); ADCs varied with tumour viability and perfusion; and SUVmax dropped at 24 h (P < 0.01). Relative K of tumour versus liver at 48 h correlated with relative vascular density on microangiography (r = 0.93, P < 0.05).

Conclusions

The imaging biomarkers allowed morphological, functional and metabolic quantifications of vascular shutdown, necrosis formation and tumour relapse shortly after treatment. A single dose of ZD6126 significantly diminished tumour blood supply and growth until 48 h post-treatment.

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Acknowledgements

This work was partially supported by the grants awarded by Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO Vlaanderen) Impulsfinanciering project (ZWAP/05/018), Geconcerteerde Onderzoeksactie (GOA) of the Flemish Government, OT project (OT/06/70) MoSAIC, the K.U. Leuven Molecular Small Animal Imaging Center (KUL EF/05/08) and a EU project Asia-Link CfP 2006-EuropeAid/123738/C/ACT/Multi-Proposal No. 128-498/111.

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Authors and Affiliations

  1. Department of Radiology, University Hospitals, University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    Huaijun Wang, Junjie Li, Feng Chen, Frederik De Keyzer, Jie Yu, Yuanbo Feng, Guy Marchal & Yicheng Ni

  2. Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, China

    Feng Chen

  3. Department of Nuclear Medicine, University Hospitals, University of Leuven, Herestraat 49, 3000, Leuven, Belgium

    Johan Nuyts

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  1. Huaijun Wang
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Correspondence to Yicheng Ni.

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Wang, H., Li, J., Chen, F. et al. Morphological, functional and metabolic imaging biomarkers: assessment of vascular-disrupting effect on rodent liver tumours. Eur Radiol 20, 2013–2026 (2010). https://doi.org/10.1007/s00330-010-1743-5

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  • DOI: https://doi.org/10.1007/s00330-010-1743-5

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