Early assessment of response to treatment in breast cancer by [18F]fluorothymidine-positron emission tomography

Abstract

2084 Background: Current radiological methods for assessing treatment response in breast cancer provide little information on tumour biology and often require several cycles of treatment before changes in tumour volume can be visualised. We assessed the feasibility of quantitative FLT-PET measurement of cellular proliferation as an early non-invasive measure of response. Methods: The relationship between FLT uptake and proliferation, reproducibility of the technique, and the effect of chemotherapy on FLT uptake were assessed in patients with primary or metastatic breast cancer. Patients with lesions ≥ 2.5 cm in diameter were eligible. Two FLT-PET scans were performed in the week prior to starting chemotherapy. Patients were then scanned one week after treatment with 5-fluorouracil 600mg/m2, epirubicin 60 mg/m2, and cyclophosphamide 600mg/m2. For PET scanning 150–370 MBq of FLT was injected i.v. followed by dynamic imaging for 90 min. Analyses of FLT and FLT glucuronide in blood were performed during the scan. Tumour regions of interest were defined and the pharmacokinetics of FLT in tissues calculated. Results: In patients with suitable histology, the kinetic parameter Ki (net irreversible transfer rate constant of FLT from plasma to tumour) correlated best with Ki-67 labelling index, a histological measure of proliferation (r=0.92, n=9 patients, p=0.0004). FLT-PET was found to be reproducible (mean Ki for scan 1 and scan 2 were 4.28±0.84 x 10-4and 3.94± 0.70 x10-4ml plasma.sec-1. ml tissue-1, respectively (p=0.09); coefficient of repeatability was 1.05. At one week post chemotherapy, 3 out of 11 patients showed an FLT-response, i.e. a significant reduction in FLT uptake from the pre-treatment value. In one patient, an FLT-response was observed in an axillary metastasis but not in the primary tumour. Conclusion: We have demonstrated the feasibility of FLT-PET to quantify early changes in tumour cell proliferation after chemotherapy in breast cancer patients. No significant financial relationships to disclose.