Background: We are currently conducting a phase I trial of PARP inhibitor, V on an intermittent (7 or 14 day) or continuous (21 day) schedule in combination with C in patients (pts) with advanced breast cancer. We are using FLT PET/CT sequentially to assess DNA damage induced by varying dose schedules of PARP inhibitor, where uptake of FLT depends on the proliferation rate of the tumor. Methods: Eligible pts received C-AUC 5 Q 3weeks (except dose level 1-AUC 6) plus escalating doses of V, BID on 7, 14, or 21-day schedules based on a standard 3+3 dose escalation design. We performed FLT PET/CT at baseline, cycle 1 day 7 and 14 and after cycle 3. Lesions were track-matched with the FDG PET/CT and semi-quantitatively assessed using 2D ROI placement in a matched, blinded fashion. Results: 38 pts have been accrued to 7 dose levels and FLT-PET imaging was successfully obtained in all pts with the proliferative whole body mapping revealing expected bone-marrow, liver and RESuptake. FLT-PET uptake showed a significant (p < 0.001) decrease between baseline and day 7 (N = 25) with an overall trend to rebound nearly to baseline at day 14 for pts that did not show a significant decrease in FLT uptake reduction after cycle 3. The 14-day (n = 15) dosing schedule resulted in more pronounced day 14 reduction in FLT uptake when compared to those on the 7-day (n = 7) schedule. A FLT rebound to baseline level appeared to be associated with limited therapy response. There were no reported toxicities from FLT imaging. Conclusions: FLT-PET was consistently obtained with excellent whole body quality. All lesions revealed a FLT (proliferation) uptake that was different from the FDG (metabolism) uptake. FLT uptake indicated an initial reduction of proliferation at day 7, followed by a rebound at day 21 in all patients on the 7 or 14 day schema. The trial protocol was therefore amended to include a 21 day schema which is currently still ongoing. FLT appears to be a promising in-vivo imaging marker that may serve as a guiding tool to optimize dosing schema in addition to assessing/ predicting overall response. Study support- U01 CA076576 /Wright Center of Innovation ODSA TECH09-028. Clinical trial information: NCT01251874.