Comparison of (18)F-FES, (18)F-FDG, and (18)F-FMISO PET Imaging Probes for Early Prediction and Monitoring of Response to Endocrine Therapy in a Mouse Xenograft Model of ER-Positive Breast Cancer

BACKGROUND: There is an increasing need to characterize biological processes for early prediction and monitoring of response to endocrine therapy in breast cancer using multiple positron emission tomography (PET) imaging probes. However, use of more than two PET tracers in a single clinical trial is quite challenging. In this study we carried out a longitudinal investigation of (18)F-FES, (18)F-FDG, and (18)F-FMISO PET imaging probes for early prediction and monitoring of response to endocrine therapy in a mouse xenograft model of estrogen receptor (ER)-positive breast cancer. METHOD: ER(+) human breast cancer ZR-75-1 models were established in female mice that were then randomly assigned to a treatment (fulvestrant, 5.0 mg/week for 21 days) or vehicle group. Micro-PET/CT imaging with (18)F-FES, (18)F-FDG, and (18)F-FMISO was performed on days 0, 3, 14, and 21 after treatment. The uptake value (percentage injected dose per gram, %ID/g) for each probe in tumor (T) tissue and contralateral muscle (M) was measured for quantitative analysis and T/M calculation. Tumor volume was measured to record tumor growth at each time point. Tumor tissues were sampled for immunohistochemical staining of ER expression. Correlations for tumor volume and ERα levels with uptake data for the probe were tested. RESULTS: Uptake data for (18)F-FES in ZR-75-1 tumor tissues corresponded well with tumor response to endocrine therapy, but not for (18)F-FDG and (18)F-FMISO, according to longitudinal micro-PET/CT imaging and quantitative correlation analysis. There was a significant positive correlation between (18)F-FES uptake and ER levels (%ID/g(max) r(2) = 0.76, P< 0.05; T/M r(2) = 0.82, P<0.05). Notably, (18)F-FES uptake on day 3 was significantly correlated with the day 21/baseline tumor volume ratio (%ID/g(max) r(2) = 0.74, P < 0.05; T/M r(2) = 0.78, P < 0.05). CONCLUSIONS: Comparison of (18)F-FES, (18)F-FDG, and (18)F-FMISO probes revealed that (18)F-FES PET/CT molecular imaging can provide a precise early prediction of tumor response to endocrine therapy in ER(+) breast cancer in a ZR-75-1 xenograft model. This molecular imaging strategy with (18)F-FES PET/CT will be useful in evaluating the efficacy of endocrine therapies and in developing new endocrine drugs.