Comparison of three-parameter kinetic model analysis to standard Patlak's analysis in 18F-FDG PET imaging of lung cancer patients

Background: Patlak's graphical analysis can provide tracer net influx constant (Ki) with limitation of assuming irreversible tracer trapping, that is, release rate constant (k(b)) set to zero. We compared linear Patlak's analysis to non-linear three-compartment three-parameter kinetic model analysis (3P-KMA) providing Ki, k(b), and fraction of free F-18-FDG in blood and interstitial volume (V-b). Methods: Dynamic PET data of 21 lung cancer patients were retrospectively analyzed, yielding for each patient an F-18-FDG input function (IF) and a tissue time-activity curve. The former was fitted with a three-exponentially decreasing function, and the latter was fitted with an analytical formula involving the fitted IF data (11 data points, ranging 7.5-57.5 min post-injection). Bland-Altman analysis was used for Ki comparison between Patlak's analysis and 3P-KMA. Additionally, a three-compartment five-parameter KMA (5P-KMA) was implemented for comparison with Patlak's analysis and 3P-KMA. Results: We found that 3P-KMA Ki was significantly greater than Patlak's Ki over the whole patient series, + 6.0% on average, with limits of agreement of +/- 17.1% (95% confidence). Excluding 8 out of 21 patients with k(b) > 0 deleted this difference. A strong correlation was found between Ki ratio (=3P-KMA/Patlak) and k(b) (R = 0.801; P < 0.001). No significant difference in Ki was found between 3P- KMA versus 5P-KMA, and between 5P-KMA versus Patlak's analysis, with limits of agreement of +/- 23.0 and +/- 31.7% (95% confidence), respectively. Conclusions: Comparison between 3P-KMA and Patlak's analysis significantly showed that the latter underestimates Ki because it arbitrarily set kb to zero: the greater the kb value, the greater the Ki underestimation. This underestimation was not revealed when comparing 5P-KMA and Patlak's analysis. We suggest that further studies are warranted to investigate the 3P-KMA efficiency in various tissues showing greater F-18-FDG trapping reversibility than lung cancer lesions.