Early Detection of Response to Experimental Chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in Human Ovary Cancer Xenografts in Mice

Background 3′-deoxy-3′-[ 18 F]fluorothymidine ( 18 F-FLT) is a tracer used to assess cell proliferation in vivo . The aim of the study was to use 18 F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of the experimental chemotherapy Top216 non-invasively by PET. Methodology/Principal Findings In vivo uptake of 18 F-FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after Top216 treatment (50 mg/kg i.v. at 0 and 48 hours) was initiated. Baseline 18 F-FLT scans were made before either Top216 (n = 7–10) or vehicle (n = 5–7) was injected and repeated after 2 and 6 hours and 1 and 5 days of treatment. A parallel study was made with 2′-deoxy-2′-[ 18 F]fluoro-D-glucose ( 18 F-FDG) (n = 8). Tracer uptake was quantified using small animal PET/CT. Imaging results were validated by tumor volume changes and gene-expression of Ki67 and TK1. Top216 (50 mg/kg 0 and 48 hours) inhibited the growth of the A2780 tumor compared to the control group (P<0.001). 18 F-FLT uptake decreased significantly at 2 hours (−52%; P<0.001), 6 hours (−49%; P = 0.002) and Day 1 (−47%; P<0.001) after Top216 treatment. At Day 5 18 F-FLT uptake was comparable to uptake in the control group. Uptake of 18 F-FLT was unchanged in the control group during the experiment. In the treatment group, uptake of 18 F-FDG was significantly decreased at 6 hours (−21%; P = 0.003), Day 1 (−29%; P<0.001) and Day 5 (−19%; P = 0.05) compared to baseline. Conclusions/Significance One injection with Top216 initiated a fast and significant decrease in cell-proliferation assessable by 18 F-FLT after 2 hours. The early reductions in tumor cell proliferation preceded changes in tumor size. Our data indicate that 18 F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients.