PET/CT images.

<p>Representative [18F]FLT PET/CT images of A2780 (upper panel), A2780/Top216 (mid panel) and SW620 (lower panel) xenografts (dotted circles). [18F]FLT uptake is measured in the same animals at baseline and 6 hours, Day 1 and Day 6 follow treatment initiation with TP202377.</p

Primer and probe sequences for the genes investigated.

<p>Primer and probe sequences for the genes investigated.</p

FLT uptakes after treatment with carboplatin and paclitaxel.

<p>FLT uptake was analyzed one hour post injection in a carboplatin/paclitaxel treatment (n=6 tumors) and a control group (n=7 tumors). The mice were PET/CT scanned at baseline before treatment start and day 1, 4 and 8 after injection of first dose. <b>A</b>) Tumor uptake of FLT during treatment of A2780 xenograft tumors with carboplatin and paclitaxel. Quantitative tumor uptake is presented as SUVmean and SUVmax (mean±SEM). <b>B</b>) Representative PET/CT images of one mouse from the carboplatin and paclitaxel treatment group (upper images) and one mouse from the control vehicle treated group (lower images). On the images of the mouse from the treatment group two tumors are visible whereas on the images of the control mouse only one tumor is visible. Dotted circles indicate the tumors.</p

Expression of Ki67 and TK1 normalized to expression of reference gene TBP.

<p>Data are presented as fold changes following treatment with Top216/vehicle relative to baseline levels (n = 7 tumors per group). Top216 treatment was initiated at 0 hours and repeated at 48 hours after the first injection. *) P<0.05, **) P<0.01, ***) P<0.001 compared to baseline.</p

Gene expression of GLUT1, HK1, HK2, Ki67 and TK1.

<p>On day 8 immediately after the last PET/CT scan all tumors were excised and total RNA was isolated and afterward revers transcribed into cDNA. With qPCR relative expression of GLUT1, HK1, HK2, Ki67 and TK1 were measured. The levels of the gene of interests were normalized to the geometric means of two reference genes GUSB and HPRT. <b>A</b>) For the FDG study GLUT1 expression was decreased, the difference not being statistically significant (p=0.08), HK1 expression was lower in the treatment compared to the control group (p=0.03). <b>B</b>) For the FLT study no difference in Ki67 and TK1 between the treatment and control group was observed on day 8. The data are presented as mean±SEM.</p

Chemical structure of Top216.

<p>Chemical structure of Top216.</p

FDG uptakes after treatment with carboplatin and paclitaxel.

<p>FDG uptake was analyzed one hour post injection in a carboplatin/paclitaxel treatment (n=8 tumors) and a control group (n=5 tumors). The mice were PET/CT scanned at baseline before treatment start and day 1, 4 and 8 after injection of first dose. <b>A</b>) Tumor uptake of FDG during treatment of A2780 xenograft tumors with carboplatin and paclitaxel. Quantitative tumor uptake is presented as SUVmean and SUVmax (mean±SEM). <b>B</b>) Representative PET/CT images of one mouse from the carboplatin and paclitaxel treatment group (upper images) and one mouse from the control vehicle treated group (lower images). Dotted circles indicate the tumors.</p

Fused PET/CT images.

<p>A) The eight images at left are representative coronal fused PET/CT images of two mice scanned with ¹⁸F-FLT at baseline and at 6 hours and 1 and 5 days after treatment start. The images at the top show one mouse treated with Top216 and the images at the bottom show one control mouse which received vehicle. The four images at right show fused PET/CT pictures of two representative mice treated with either Top216 or vehicle and scanned at baseline and 2 hours after treatment initiation. The arrows point towards the tumors. B) Representative coronal fused PET/CT images of two mice scanned with ¹⁸F-FDG at baseline and 6 hours and 1 and 5 days after treatment start. The images at the top show one mouse treated with Top216 and the images at the bottom show one control mouse which received vehicle. The arrows point towards the tumors.</p

Schematic view of the experimental design.

<p>Schematic view of the experimental design.</p

Primer sequences for Ki67, TK1 and reference genes.

<p>Primer sequences for Ki67, TK1 and reference genes.</p