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Kinetic modeling of 3'-deoxy-3'-18F-fluorothymidine for quantitative cell proliferation imaging in subcutaneous tumor models in mice

Cited 37 time in Web of Science Cited 37 time in Scopus
Authors
Kim, Su Jin; Lee, Jae Sung; Im, Ki Chum; Kim, Seog-Young; Park, Soo-Ah; Lee, Seung Jin; Oh, Seung Jun; Lee, Dong Soo; Moon, Dae Hyuk
Issue Date
2008-11-11
Publisher
The Society of Nuclear Medicine Inc
Citation
J Nucl Med. 2008;49(12):2057-2066
Keywords
AnimalsCell Line, TumorCell ProliferationComputer SimulationDideoxynucleosides/*diagnostic use/*pharmacokineticsImage Interpretation, Computer-Assisted/methodsKineticsMetabolic Clearance RateMiceMice, Inbred BALB CMice, Inbred C57BLMice, Nude*Models, BiologicalRadiopharmaceuticals/diagnostic use/pharmacokineticsSkin/*metabolism/*radionuclide imagingSkin Neoplasms/*metabolism/*radionuclide imaging
Abstract
3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-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 (18)F-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 (18)F-FLT injection. In parallel, dynamic (18)F-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 (18)F-FLT in human epithelial carcinoma (A431) and Lewis lung carcinoma tumor models in mice. Three-compartment models with reversible phosphorylation (k(4) not equal 0, 3C5P) and irreversible phosphorylation (k(4) = 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-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: (18)F-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-activity curves for tumor regions. The net influx of (18)F-FLT (K(FLT)) and k(3) obtained with this model showed reasonable intersubject variability and discrimination ability for tumor models with different proliferation properties. The K(FLT) 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 (18)F-FLT PET in mice, and kinetic modeling analysis with an adequate compartment model provided reliable kinetic parameters for measuring tumor proliferation.
ISSN
0161-5505 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18997037

http://jnm.snmjournals.org/cgi/reprint/49/12/2057.pdf

http://hdl.handle.net/10371/67792
DOI
https://doi.org/10.2967/jnumed.108.053215
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College of Medicine/School of Medicine (의과대학/대학원)Nuclear Medicine (핵의학전공)Journal Papers (저널논문_핵의학전공)
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