18FFDG and 18FFLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in miceReportar como inadecuado




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BMC Cancer

, 13:168

Experimental therapeutics and drug development

Abstract

BackgroundBelinostat 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’-Ffluorothymidine 18FFLT and 2-deoxy-2-Ffluoro-D-glucose 18FFDG positron emission tomography PET following treatment with belinostat in ovarian cancer in vivo models.

MethodsIn vivo uptake of 18FFLT and 18FFDG 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 18FFLT or 18FFDG scans were made before treatment Day 0 and repeated at Day 3, 6 and 10. Tracer uptake was quantified using small animal PET-CT.

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

Conclusions18FFDG uptake early following treatment initiation predicted tumor sizes at Day 10, suggesting that 18FFDG may be a valuable biomarker for non-invasive assessment of anti-tumor activity of belinostat.

KeywordsPositron emission tomography PET Belinostat Histone deacetylase inhibitor 18FFLT 18FFDG Computed tomography CT Abbreviations18FFLT3’-deoxy-3’-Ffluorothymidine

18FFDG2-deoxy-2-Ffluoro-D-glucose

PETPositron emission tomography

CTComputed tomography

TK1Thymidine kinase 1

HDACHistone deacetylase

ROIsRegion of interests

SUVStandard uptake value

GOIGene of interests

TSThymidylate synthease

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-13-168 contains supplementary material, which is available to authorized users.

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Autor: Mette Munk Jensen - Kamille Dumong Erichsen - Camilla Bardram Johnbeck - Fredrik Björkling - Jacob Madsen - Peter Buhl 

Fuente: https://link.springer.com/







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