Repeatability of quantitative ¹⁸F-FLT uptake measurements in solid tumors: an individual patient data multi-center...

3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative ¹⁸F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of ¹⁸F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts.

A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five ¹⁸F-FLT repeatability cohorts in solid tumors. ¹⁸F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUV_max, SUV_mean, SUV_peak, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated.

Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all ¹⁸F-FLT uptake metrics (R² ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUV_peak (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUV_max ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics.

In multi-center studies, differences ≥ 25% in ¹⁸F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied.