Changes in 18F-FDG uptake within minutes after chemotherapy in a rabbit VX2 tumor model

The purpose of this study was to investigate whether (18)F-FDG PET/CT can be used for in vivo chemosensitivity testing and to determine the optimal time point for observation.

Forty-two rabbits with 84 implanted VX2 squamous cell tumors were randomized into a control group (n = 10) and a treatment group (n = 32). (18)F-FDG PET/CT was performed the day before intravenous administration of cisplatin (4 mg/kg) and at 95-100 min (day 0), day 1, day 7, and day 14 afterward. In the control group, (18)F-FDG PET/CT images were acquired at the same time points but without cisplatin administration. Maximum standardized uptake value (SUV) and mean SUV were analyzed. On the basis of tumor volume, we categorized animal tumors into a sensitive group and an insensitive group. If tumor volume doubled by day 7, the tumor was considered insensitive.

On day 0, maximum SUV and mean SUV were significantly different between the sensitive group and the insensitive and control groups (P < 0.05 for both). In the sensitive group, the average change from the pretherapy values was -48.96% +/- 12.27% for maximum SUV and -51.63% +/- 10.45% for mean SUV. SUV did not significantly differ between the groups at any other points (days 1-14). On day 0, tumor volume was not significantly different between the control group and the sensitive or insensitive groups. After cisplatin administration, the size of the VX2 xenograft tumors increased slowly. Tumor necrosis fractions on days 7 and 14 were significantly greater in the sensitive group than in the insensitive or control group. Viable tumor cells on days 7 and 14 were less numerous in the sensitive group than in the insensitive or control group. A significant difference in inflammatory cells was seen between the sensitive and insensitive groups on days 7 and 14 (P < 0.05 for both). No significant differences in inflammatory cells or viable tumor cells were seen between the insensitive and control groups at any time points from before therapy to day 14 (P > 0.05 for all). A slight increase in viable tumor cells and inflammatory cells was seen in the sensitive group on day 14, compared with day 7.

When (18)F-FDG was injected as early as 40 min after administration of chemotherapy, PET showed significantly decreased in vivo uptake of the tracer in chemoresponsive tumors. This finding suggests that (18)F-FDG PET may be able to discriminate sensitive from insensitive tumors if the imaging is performed immediately after a test dose of chemotherapy. The optimal observation time and methodology for various chemotherapy-tumor combinations will need to be studied to confirm whether this approach can be generalized.