Does measurement of 18F-fluoride metabolic flux improve response assessment of breast cancer bone metastases compared with standardised uptake values in 18F-fluoride PET/CT?

Purpose: To establish whether non-invasive measurement of changes in 18F-fluoride metabolic flux to bone mineral (Ki) by positron emission tomography/ computed tomography (PET/CT) can provide incremental value in response assessment of bone metastases in breast cancer compared to maximum and mean standardized uptake values (SUVmax, SUVmean). Methods: Twelve breast cancer patients starting endocrine treatment for de-novo or progressive bone metastases were included. Static 18F-fluoride PET/CT scans were acquired 60 minutes post-injection, before and 8 weeks after commencing treatment. Venous blood samples were taken at 55 and 85 minutes post-injection to measure plasma 18F-fluoride activity concentrations. This allowed calculation of Ki in individual bone metastases using a previously validated method. Percentage changes in Ki, SUVmax and SUVmean were calculated from the same ≤ 5 index lesions from each patient. Clinical response up to 24 weeks, assessed in consensus by two experienced oncologists blinded to PET imaging findings, was used as a reference standard. Results: In the 4 patients with clinical progressive disease (PD), mean Ki significantly increased (>25%) in all, SUVmax in 3 and SUVmean in 2. In the 8 non-PD patients, Ki decreased or remained stable in 7, SUVmax in 5 and SUVmean in 6. A significant mean percentage increase in Ki from baseline occurred in the 4 patients with PD compared with SUVmax and SUVmean (89.7% vs 41.9% and 43.8%, respectively; p<0.001). Conclusion: After 8 weeks of endocrine treatment for bone-predominant metastatic breast cancer, Ki more reliably differentiated PD from non-PD than SUVmax and SUVmean, probably because measurement of SUVs underestimates fluoride clearance as changes in input function are not accounted for.