Monitoring Preclinical Model of Breast Cancer with [18F]FLT AND [18F]FDG-PET.

Aim: The thymidine analogue FLT seems to be more efficient than FDG in the early prediction of response to chemotherapeutics acting on cell proliferation like antitubulin drugs. The aim of this study was to compare the tumor uptake of [18F]FLT and [18F]FDG in a preclinical model of breast cancer in response to Paclitaxel. Materials and methods: SCID mice were subcutaneously implanted with 1.5 x 107 MDA-MB-468 cells. Lesion's size were constantly monitored with calliper and volumes calculated as (L x l2)/2 mm3. When tumours were approximately 75 mm3, animals underwent basal [18F]FDG and [18F]FLT-PET (PET I) and were treated for two weeks with Paclitaxel or vehicle (n=4 each group; 18 mg/kg i. v.; two doses per weeks). At the end of treatment, mice underwent the second [18F]FDG and [18F]FLT-PET (PET II) and were sacrificed for in vitro examination of tumor (H&E staining and Ki-67 binding). The experiment was repeated with additional animals having an initial lesion volume of approximately 250 mm3. PET images were calibrated, corrected for the isotope half life and elaborated with PMOD software to calculate: 1) Standardized Uptake Value (SUVmax); 2) [18F]FDG and [18F]FLT metabolic volume and 3) total lesion proliferation/glycolysis index (SUVmean x metabolic volume). Results: In the first experiment, no increase in lesion volume was observed in treated group between PET I and PET II whereas in controls a 4-fold increased was present (p<0.05). SUVmax in basal PET was ranging between 1.0 to 1.5 for [18F]FLT and 0.6 to 0.9 for [18F]FDG. Treatment reduced both [18F]FLT and [18F]FDG SUVmax values of 38% (p<0.01). No significant modifications were observed for [18F]FLT and [18F]FDG metabolic volume and total lesion proliferation/glycolysis although a trend to a decrement of both variable was observed in the treated group. Finally we observed a good correlation (r2>0.73, p<0.01) between SUVmax and tumor volume in treated but not in controls for both radioligands. This correspondence and treatment effects on SUVmax was lost considering animals with initial large lesions. Histology and Ki-67 binding shown not significant differences in growth pattern of treated versus vehicle animals. Conclusion: Paclitaxel, with its anti-replicative mechanism, reduces tumor progression in terms of lesion size and [18F]FLT/[18F]FDG uptake when initial volume was limited (<100 mm3). The reason of the lack of response in the second experiment deserve further investigations. Acknowledgements: This research has been supported by AIRC Project Molecular and Cellular Imaging of Cancer and by PIO Project PET Molecular Imaging.