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Open Access Highly Accessed Research article

[18F]FDG and [18F]FLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in mice

Mette Munk Jensen12*, Kamille Dumong Erichsen3, Camilla Bardram Johnbeck12, Fredrik Björkling34, Jacob Madsen2, Peter Buhl Jensen3, Maxwell Sehested3, Liselotte Højgaard12 and Andreas Kjær12

Author Affiliations

1 Cluster for Molecular Imaging, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 12.3.11, Copenhagen N, 2200, Denmark

2 Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Denmark

3 Topotarget A/S, Symbion Science Park, Fruebjergvej 3, Copenhagen, 2100, Denmark

4 Present address: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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BMC Cancer 2013, 13:168  doi:10.1186/1471-2407-13-168

Published: 1 April 2013

Abstract

Background

Belinostat is a histone deacetylase inhibitor with anti-tumor effect in several pre-clinical tumor models and clinical trials. The aim of the study was to evaluate changes in cell proliferation and glucose uptake by use of 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) following treatment with belinostat in ovarian cancer in vivo models.

Methods

In vivo uptake of [18F]FLT and [18F]FDG in human ovary cancer xenografts in mice (A2780) were studied after treatment with belinostat. Mice were divided in 2 groups receiving either belinostat (40 mg/kg ip twice daily Day 0–4 and 6–10) or vehicle. Baseline [18F]FLT or [18F]FDG scans were made before treatment (Day 0) and repeated at Day 3, 6 and 10. Tracer uptake was quantified using small animal PET/CT.

Results

Tumors in the belinostat group had volumes that were 462 ± 62% (640 mm3) at Day 10 relative to baseline which was significantly different (P = 0.011) from the control group 769 ± 74% (926 mm3). [18F]FLT SUVmax increased from baseline to Day 10 (+30 ± 9%; P = 0.048) in the control group. No increase was observed in the treatment group. [18F]FDG SUVmean was significantly different in the treatment group compared to the control group (P = 0.0023) at Day 10. Within treatment groups [18F]FDG uptake and to a lesser extent [18F]FLT uptake at Day 3 were significantly correlated with tumor growth at Day 10.

Conclusions

[18F]FDG uptake early following treatment initiation predicted tumor sizes at Day 10, suggesting that [18F]FDG may be a valuable biomarker for non-invasive assessment of anti-tumor activity of belinostat.

Keywords:
Positron emission tomography (PET); Belinostat; Histone deacetylase inhibitor; [18F]FLT; [18F]FDG; Computed tomography (CT)