Evaluation of limited blood sampling population input approaches for kinetic quantification of [18F]fluorothymidine PET data

Background: Quantification of kinetic parameters of positron emission tomography (PET) imaging agents normally requires collecting arterial blood samples which is inconvenient for patients and difficult to implement in routine clinical practice. The aim of this study was to investigate whether a population-based input function (POP-IF) reliant on only a few individual discrete samples allows accurate estimates of tumour proliferation using [F-18]fluorothymidine (FLT). Methods: Thirty-six historical FLT-PET data with concurrent arterial sampling were available for this study. A population average of baseline scans blood data was constructed using leave-one-out cross-validation for each scan and used in conjunction with individual blood samples. Three limited sampling protocols were investigated including, respectively, only seven (POP-IF7), five (POP-IF5) and three (POP-IF3) discrete samples of the historical dataset. Additionally, using the three-point protocol, we derived a POP-IF3M, the only input function which was not corrected for the fraction of radiolabelled metabolites present in blood. The kinetic parameter for net FLT retention at steady state, K-i, was derived using the modified Patlak plot and compared with the original full arterial set for validation. Results: Small percentage differences in the area under the curve between all the POP-IFs and full arterial sampling IF was found over 60 min (4.2%-5.7%), while there were, as expected, larger differences in the peak position and peak height. A high correlation between K-i values calculated using the original arterial input function and all the population-derived IFs was observed (R-2 = 0.85-0.98). The population-based input showed good intra-subject reproducibility of K-i values (R-2 = 0.81-0.94) and good correlation (R-2 = 0.60-0.85) with Ki-67. Conclusions: Input functions generated using these simplified protocols over scan duration of 60 min estimate net PET-FLT retention with reasonable accuracy.