Abstract 5320: Changes in [18]F-FLT and [18]F-FDG positron emission tomography following treatment with belinostat alone and in combination with paclitaxel/carboplatin in human ovary cancer xenografts in mice

Abstract

Abstract Introduction: 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 early changes in cell proliferation and glucose uptake by use of 3’-deoxy-3’-[18F]fluorothymidine (FLT) and 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) following treatment with belinostat alone or in combination with carboplatin and paclitaxel (CaP). Methods: In vivo uptake of FLT and FDG in human ovary cancer xenografts in mice (A2780) was studied after treatment initiation. When tumor volumes were approximately 100 mm3 mice were divided in 4 groups receiving belinostat, CaP, combination of these (BelCaP) or vehicle. Doses were 40 mg/kg ip twice daily for 10 days for belinostat, 10 mg/kg iv day 2+9 for paclitaxel and 40 mg/kg ip day 2+9 for carboplatin. Baseline FLT or FDG scans were made before treatment day 0 and repeated at day 3, 6 and 10. FLT uptake was quantified using small animal PET/CT. One hour after iv injection of 10 MBq FLT or FDG, PET scans were performed for 10 minutes and region of interests (ROIs) covering whole tumor were defined on PET/CT images for calculation of standard uptake values (SUV). Results: Tumors in the control group had volumes that were 769±74% (926 mm3) at day 10 relative to baseline day 0. In the belinostat group tumors were 462±62 % (640 mm3) (P=0.004 vs. control), in the CaP group 359±41% (490 mm3) (P<0.001 vs. control), and in the BelCaP group 332±35% (341 mm3) (P<0.001 vs. control) all at day 10 relative to baseline. On day 10 FLT SUVmax was significantly lower in the CaP group (−21.5%; P<0.05) and BelCaP group (−35.6%; P<0.001) compared to control. On day 3 FLT SUVmax was significantly lower for the CaP (−23.4%; P<0.05) and the BelCaP group (−22.1%; P<0.05) compared to the Belinostat group. On day 10 FDG SUVmax was significantly decreased in the belinostat group (−22.4%; P<0.05), the CaP group (−27.4%; P<0.01) and the BelCaP combination group (−29.1%; P<0.001) compared to control. Within treatment groups FLT SUVmean day 3 was significantly correlated with relative tumor volume day10/day0 in the belinostat group (R2=0.67; P=0.025) but not in the CaP and BelCaP groups. FDG SUVmean day 3 was not correlated with relative tumor volume day10/day0 in any of the treatment groups, however FDG SUVmean day 6 correlated significantly with tumor volume day10/day0 in the belinostat group (R2=0.68; P=0.023). Conclusions: In the belinostat group FLT uptake day 3 and FDG uptake day 6 predicted relative tumor volume changes at day 10. FDG uptake was significantly decreased day 10 for all treatment groups compared to control. Our data indicate that FLT and FDG PET may be used for non-invasive assessment of anti-tumor effects of belinostat both alone and in combination with carboplatin and paclitaxel. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5320. doi:10.1158/1538-7445.AM2011-5320