1. [18F]FDG and [18F]FLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in mice.
- Author
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Jensen MM, Erichsen KD, Johnbeck CB, Björkling F, Madsen J, Jensen PB, Sehested M, Højgaard L, and Kjær A
- Subjects
- Animals, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Disease Models, Animal, Female, Glucose Transporter Type 1 genetics, Humans, Hydroxamic Acids administration & dosage, Hydroxamic Acids therapeutic use, Ki-67 Antigen genetics, Mice, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Radiopharmaceuticals, Sulfonamides administration & dosage, Sulfonamides therapeutic use, Thymidine Kinase genetics, Tumor Burden, Dideoxynucleosides, Fluorodeoxyglucose F18, Ovarian Neoplasms diagnosis, Positron-Emission Tomography
- 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'-[(18)F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[(18)F]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 mm(3)) at Day 10 relative to baseline which was significantly different (P = 0.011) from the control group 769 ± 74% (926 mm(3)). [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.
- Published
- 2013
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