Imaging early changes in proliferation at 1 week post chemotherapy:: a pilot study in breast cancer patients with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography

Purpose 3'-Deoxy-3'-[F-18]fluorothymidine positron emission tomography ([F-18]FLT-PET) has been developed for imaging cell proliferation and findings correlate strongly with the Ki-67 labelling index in breast cancer. The aims of this pilot study were to define objective criteria for [F-18]FLT response and to examine whether [F-18]FLT-PET can be used to quantify early response of breast cancer to chemotherapy. Methods Seventeen discrete lesions in 13 patients with stage II-IV breast cancer were scanned prior to and at 1 week after treatment with combination 5-fluorouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. The uptake at 90 min (SUV90) and irreversible trapping (K-i) of [1(8)F]FLT were calculated for each tumour. The reproducibility of [F-18]FLT-PET was determined in nine discrete lesions from eight patients who were scanned twice before chemotherapy. Clinical response was assessed at 60 days after commencing FEC. Results All tumours showed [F-18]FLT uptake and this was reproducible in serial measurements (SD of mean % difference = 10.5% and 15.1%, for SUV90 and K-i, respectively; test-retest correlation coefficient >= 0.97). Six patients had a significant clinical response (complete or partial) at day 60; these patients also had a significant reduction in [F-18]FLT uptake at 1 week. Decreases in K (i) and SUV90 at 1 week discriminated between clinical response and stable disease (p = 0.022 for both parameters). In three patients with multiple lesions there was a mixed [F-18]FLT response in primary tumours and metastases. [F-18]FLT response generally preceded tumour size changes. Conclusion [F-18]FLT-PET can detect changes in breast cancer proliferation at 1 week after FEC chemotherapy.