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J Nucl Med. 2008; 49 (Supplement 1):151P
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Instrumentation & Data Analysis: Data Analysis & Management

Cardiac/Small Animal

Comparison of methodologies for quantitative analysis of [18F]FLT PET in tumor xenografts in mice

Su Jin Kim1, Jae Sung Lee1, Ki Chun Im2, Seog-Young Kim2, Soo-Ah Park2, Seung Jin Lee2, Dong Soo Lee1 and Dae Hyuk Moon2

1 Dept of Nuclear Medicine, Seoul National U Coll of Medicine, Seoul, South Korea; 2 Dept of Nuclear Medicine, U of Ulsan, Seoul, South Korea

603

Objectives: Although 3'-deoxy-3'-18F-fluorothymidine (FLT) PET studies have been performed in various tumor models in mice, only the semi-quantitative approaches were used. The aim of this study was to compare the methodologies for the quantitative FLT PET studies in tumor xenografts in mice.

Methods: We investigated the kinetic models of FLT in A431 (n=7) and LLC (n=10) tumor xenografts. PET scans were acquired for 2 hours. Goodness-of-fit for tissue time activity curves (CT) using 3-compartment models with reversible (3C5P) and irreversible phosphorylation (3C4P) was compared. The effects of incorporating blood volume fraction (Vb) in the model were also tested. Several macro parameters associated with FLT metabolism, such as net influx rate (KFLT), total distribution volume (DVtot), and DV of FLT phosphorylated nucleotides (DVm), were explored. Patlak graphical analysis (PGA) was performed and SUV was also calculated. These parameters were compared to the results of Ki-67 immunohistochemical analysis and thymidine kinase assay.

Results: 3C5P model was best to describe the CT and the curve fitting was more accurate when Vb term was included. KFLT was significantly underestimated with 3C4P model or PGA. The A431 and LLC tumors showed markedly different levels of the PET parameters (k3, k3/k4, KFLT, DVm, DVtot, and SUV), which agree with the ex vivo analysis results. KFLT-3C5P, that showed smallest variability among the macro parameters, strongly correlated with k3 but was not dominated by K1.

Conclusions: The 3-compartment model with reversible phosphorylation and variable Vb was best to describe the FLT kinetics in mice. Kinetic modeling analysis with this model provided reliable kinetic parameters to measure the tumor proliferation.





This Article
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Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Kim, S. J.
Right arrow Articles by Moon, D. H.
PubMed
Right arrow Articles by Kim, S. J.
Right arrow Articles by Moon, D. H.