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

BMC Cancer

Andreas Kjær¹  Liselotte Højgaard¹  Maxwell Sehested²  Peter Buhl Jensen²  Jacob Madsen¹  Fredrik Björkling³  Camilla Bardram Johnbeck¹  Kamille Dumong Erichsen²  Mette Munk Jensen¹ 

[1]Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Denmark

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

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

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

Others  :  1079822
DOI  :  10.1186/1471-2407-13-168

 received in 2012-09-05, accepted in 2013-03-20,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Munk Jensen et al.; licensee BioMed Central Ltd.

【 图 表 】

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