TY - JOUR

T1 - Relative Strengths of Three Linearizations of Receptor Availability

T2 - Saturation, Inhibition, and Occupancy Plots

AU - Khodaii, Javad

AU - Araj-Khodaei, Mostafa

AU - Vafaee, Manouchehr S.

AU - Wong, Dean F.

AU - Gjedde, Albert

N1 - Publisher Copyright: © 2022 by the Society of Nuclear Medicine and Molecular Imaging.

PY - 2022

Y1 - 2022

N2 - We derived three widely used linearizations from the definition of receptor availability in molecular imaging with positron emission tomography (PET). The purpose of the present research was to determine the convergence of the results of the 3 methods in terms of 3 parameters-occupancy (s), distribution volume of the nondisplaceable reference binding compartment (VND), and nondisplaceable reference binding potential (BPND) of the radioligand-in the absence of a gold standard. We tested 104 cases culled from the literature and calculated the goodness of fit of the least-squares and Deming II methods of linear regression when applied to the determination of s, VND, and BPND using the goodness-of-fit parameters R2, coefficient of variation (root-mean-square error [RMSE]), and the infinity norm (‖X‖∞) with both regression methods. We observed superior convergence among the values of s, VND, and BPND for the inhibition and occupancy plots. The inhibition plot emerged as the plot with a slightly higher degree of convergence (based on R2, RMSE, and ‖X‖∞ value). With two regression methods (the least-squares method [LSM] and the Deming II [DM] method), the estimated values of s, VND, and BPND generally converged. The inhibition and occupancy plots yielded the best fits to the data, according to the goodness-of-fit parameters, due primarily to absence of commingling of the dependent and independent variables tested with the saturation (original Lassen) plot. In the presence of noise, the inhibition and occupancy plots yielded higher convergences.

AB - We derived three widely used linearizations from the definition of receptor availability in molecular imaging with positron emission tomography (PET). The purpose of the present research was to determine the convergence of the results of the 3 methods in terms of 3 parameters-occupancy (s), distribution volume of the nondisplaceable reference binding compartment (VND), and nondisplaceable reference binding potential (BPND) of the radioligand-in the absence of a gold standard. We tested 104 cases culled from the literature and calculated the goodness of fit of the least-squares and Deming II methods of linear regression when applied to the determination of s, VND, and BPND using the goodness-of-fit parameters R2, coefficient of variation (root-mean-square error [RMSE]), and the infinity norm (‖X‖∞) with both regression methods. We observed superior convergence among the values of s, VND, and BPND for the inhibition and occupancy plots. The inhibition plot emerged as the plot with a slightly higher degree of convergence (based on R2, RMSE, and ‖X‖∞ value). With two regression methods (the least-squares method [LSM] and the Deming II [DM] method), the estimated values of s, VND, and BPND generally converged. The inhibition and occupancy plots yielded the best fits to the data, according to the goodness-of-fit parameters, due primarily to absence of commingling of the dependent and independent variables tested with the saturation (original Lassen) plot. In the presence of noise, the inhibition and occupancy plots yielded higher convergences.

KW - binding potential

KW - inhibition plot

KW - Lassen plots

KW - PET

U2 - 10.2967/jnumed.117.204453

DO - 10.2967/jnumed.117.204453

M3 - Journal article

C2 - 34088774

AN - SCOPUS:85123969025

VL - 63

SP - 294

EP - 301

JO - The Journal of Nuclear Medicine

JF - The Journal of Nuclear Medicine

SN - 0161-5505

IS - 2

ER -