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Kinetic Analysis of 3'-Deoxy-3'-Fluorothymidine PET Studies: Validation Studies in Patients with Lung Cancer

¹ Department of Radiology, University of Washington, Seattle, Washington
² Department of Pathology, University of Washington, Seattle, Washington

View larger version (12K): [in a new window]   FIGURE 1. Kinetic model of FLT metabolism is comprised of an exchangeable tissue compartment and a compartment of trapped FLT phosphate nucleotides. Four rate constants describe kinetic transfer rates between the 2 compartments. FLTMP = FLT-monophosphate; FLTDP = FLT-diphosphate; FLTTP = FLT-triphosphate; FLT-gluc = FLT-glucuronide; Qe = exchangeable tissue compartment; Qm = compartment of trapped FLT phosphorylated nucleotides; CpFLT = concentration of FLT in arterial plasma; Cmet = concentration of metabolites in arterial plasma.

View larger version (13K): [in a new window]   FIGURE 2. Blood sampling for FLT was acquired through either venous or arterial catheters at various times after injection. (A) Several patients (n = 6) had both blood and plasma activity determined from each sample. (B) Activity in blood after injection of 18F-FLT is comprised of both FLT and a labeled metabolite (FLT-glucuronide) determined by an independent assay. (C) Combining total activity in blood and the FLT fraction permits generation of an input function for FLT used to quantitate FLT tissue retention. %ID/g = percentage injected dose per gram.

View larger version (50K): [in a new window]   FIGURE 3. Three tissue types were investigated for FLT uptake. (A) Example of patient tissue time–activity curves decay corrected to time of injection. (B) Patient PET image acquired 30–60 min after injection of 118.4 MBq FLT. (C) Graphical analysis plot of normalized tissue uptake vs. normalized time for marrow, tumor, and muscle. (D) CT image close to PET image slice provides information for ROI placement and determination of recovery coefficients for tumor regions. Patient’s arms are not in field of view for standard CT protocol.

View larger version (15K): [in a new window]   FIGURE 4. Estimated KFLT value from 1 h of imaging and blood data using 3P model show high correlation with KFLT estimates using 4P model (r = 0.95; n = 18). The 60-min determination that ignores k4 consistently underestimated the KFLT value determined using more data and the 4P model.

View larger version (12K): [in a new window]   FIGURE 5. Ki-67 LI determination from tissue biopsy specimens allows for independent assessment of cellular proliferation. Plot of FLT flux determined from 4P model vs. Ki-67 LI shows high degree of correlation ( = 0.92), suggesting that use of FLT is appropriate for noninvasive estimation of cellular proliferation.