Tikhonov regularized gamma variate fits to radiochelated-DTPA bolus dilution curves with minimum plasma-clearance relative error

Objectives The Tk-GV model fits Gamma Variates to data by Tikhonov regularization with shrinkage constant, λ, chosen to minimize the relative error in plasma clearance, G (ml/min).

Methods Four statistical tests explored Tk-GV fits to bolus-dilution of ¹⁶⁹Yb-DTPA (n=41, 8 samples, 10-240 min) and ^99mTc-DTPA (n=5, 9 samples, 5-180 min), with comparison to one and two exponential term (E₁ and E₂) models with respect to: (1) physicality of ranges of model parameters, (2) effects on parameter values when different subsets of the data are fit, (3) characterization of Tk-GV residuals, and (4) extrapolative error and agreement with published correction factors.

Results Test 1 showed the GV power function exponent to be 0.59<α<0.99, n=46, where α=1 corresponds to G=0 and no late-time concentration gradient between plasma and interstitium. Test 2 showed that the Tk-GV model is best applied with 7 or more samples from 5-10 minutes to 3 or more hours. Test 3 showed G and λ to vary inversely. Test 4 showed G_Tk-GV clearance values did not need correction, agreed with published plasma clearance corrections with the general result that G_E1>G_E2>G_Tk-GV and finally that G_Tk-GV were significantly (P<0.05) more precise and accurate than G_E2.

Conclusions G_Tk-GV should replace the use of G_E2.

Research Support Partial support by grant HIC-07.49 from the Eastern Health Foundation