Reproducibility of quantitative 18F-3'-deoxy-3'-fluorothymidine measurements using positron emission tomography

Positron emission tomography (PET) using F-18-3'-deoxy-3'-fluorothymidine ([F-18]FLT) allows noninvasive monitoring of tumour proliferation. For serial imaging in individual patients, good reproducibility is essential. The purpose of the present study was to evaluate the reproducibility of quantitative [F-18]FLT measurements. Nine patients with non-small-cell lung cancer (NSCLC) and six with head-and-neck cancer (HNC) underwent [F-18]FLT PET twice within 7 days prior to therapy. The maximum pixel value (SUVmax) and a threshold defined volume (SUV41%) were defined for all delineated lesions. The plasma to tumour transfer constant (K-i) was estimated using both Patlak graphical analysis and nonlinear regression (NLR). NLR was also used to estimate k(3), which, at least in theory, selectively reflects thymidine kinase 1 activity. The level of agreement between test and retest values was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. All primary tumours and > 90% of clinically suspected locoregional metastases could be delineated. In total, 24 lesions were defined. NLR-derived K-i, Patlak-derived K-i, SUV41% and SUVmax showed excellent reproducibility with ICCs of 0.92, 0.95, 0.98 and 0.93, and SDs of 16%, 12%, 7% and 11%, respectively. Reproducibility was poor for k(3) with an ICC of 0.43 and SD of 38%. Quantitative [F-18]FLT measurements are reproducible in both NSCLC and HNC patients. When monitoring response in individual patients, changes of more than 15% in SUV41%, 20-25% in SUVmax and Patlak-derived K-i, and 32% in NLR3k-derived K-i are likely to represent treatment effects.