@article {Kim2057, author = {Su Jin Kim and Jae Sung Lee and Ki Chum Im and Seog-Young Kim and Soo-Ah Park and Seung Jin Lee and Seung Jun Oh and Dong Soo Lee and Dae Hyuk Moon}, title = {Kinetic Modeling of 3'-Deoxy-3'-18F-Fluorothymidine for Quantitative Cell Proliferation Imaging in Subcutaneous Tumor Models in Mice}, volume = {49}, number = {12}, pages = {2057--2066}, year = {2008}, doi = {10.2967/jnumed.108.053215}, publisher = {Society of Nuclear Medicine}, abstract = {3'-Deoxy-3'-18F-fluorothymidine (18F-FLT) is a thymidine analog that was developed for measuring tumor proliferation with PET. The aim of this study was to establish a kinetic modeling analysis method for quantitative 18F-FLT PET studies in subcutaneous tumor models in mice. Methods: To explore the validity of an image-derived left ventricular input function, we measured equilibrium constants for plasma and whole blood and metabolite fractions in blood after 18F-FLT injection. In parallel, dynamic 18F-FLT PET scans were acquired in 24 mice with a small-animal dedicated PET scanner to compare arterial blood activities obtained by PET and blood sampling. We then investigated kinetic models for 18F-FLT in human epithelial carcinoma (A431) and Lewis lung carcinoma tumor models in mice. Three-compartment models with reversible phosphorylation (k4 /= 0, 3C5P) and irreversible phosphorylation (k4 = 0, 3C4P) and a 2-compartment model (2C3P) were examined. The Akaike information criterion and F statistics were used to select the best model for the dataset. Gjedde{\textendash}Patlak graphic analysis was performed, and standardized uptake values in the last frame were calculated for comparison purposes. In addition, quantitative PET parameters were compared with Ki-67 immunostaining results. Results: 18F-FLT equilibrated rapidly (within 30 s) between plasma and whole blood, and metabolite fractions were negligible during PET scans. A high correlation between arterial blood sampling and PET data was observed. For 120-min dynamic PET data, the 3C5P model best described tissue time{\textendash}activity curves for tumor regions. The net influx of 18F-FLT (KFLT) and k3 obtained with this model showed reasonable intersubject variability and discrimination ability for tumor models with different proliferation properties. The KFLT obtained from the 60- or 90-min data correlated well with that obtained from the 120-min data as well as with the Ki-67 results. Conclusion: The image-derived arterial input function was found to be feasible for kinetic modeling studies of 18F-FLT PET in mice, and kinetic modeling analysis with an adequate compartment model provided reliable kinetic parameters for measuring tumor proliferation.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/49/12/2057}, eprint = {https://jnm.snmjournals.org/content/49/12/2057.full.pdf}, journal = {Journal of Nuclear Medicine} }