Analysis of three- and four-compartment models for in vivo radioligand- neuroreceptor interaction

MaRDI QIDQ1091968zbMATH OpenFDO

Authors Barry R. Zeeberg, Henry N. jun. Wagner

Publication date 1987

Published in Bulletin of Mathematical Biology (Search for Journal in Brave)

zbMATH Keywords

four-compartment modelkinetic datamacroscopic rate constantsmicroscopic rate constantsPETpositron emission tomographyradioligand-neuroreceptor interactionsthree-compartment models

Mathematics Subject Classification ID

Probabilistic models, generic numerical methods in probability and statistics (65C20) Medical applications (general) (92C50) Physiological, cellular and medical topics (92Cxx) Control/observation systems governed by ordinary differential equations (93C15)

Review text

Currently applied three-compartment models for analyzing kinetic data derived from in vivo positron emission tomographic (PET) studies of radioligand-neuroreceptor interactions require assumptions which may not be strictly valid. Such assumptions include very rapid kinetics for nonspecific binding and the absence of multiple specific receptors or subtypes. Computer simulations, based on an exact analytical solution of the relevant differential equations, indicate the numerical errors that can arise when the assumptions are invalid. We propose a four-compartment model which requires fewer assumptions. A simple relationship is derived for expressing the microscopic rate constants of either the three- or four-compartment model as explicit functions of the experimentally-observed macroscopic rate constants. This could eliminate the need for time-consuming, iterative, non-linear, curve-fitting approaches and numerical integration. The usefulness of the four-compartment model is limited, however, by the sensitivity and temporal resolution of current PET imaging devices.

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Cited in

(5)

• Theoretical effects of radioligand diffusional gradients and microscopic neuroreceptor distribution in in vivo kinetic studies
• Analysis of compartmental models of ligand-induced endocytosis
• Stochastic dynamic model for estimation of rate constants and their variances from noisy and heterogeneous PET measurements
• BIOLOGICAL RECEPTORS: IMPLICATIONS OF RADIOLIGAND QUALITY IN BINDING ASSAYS
• Reducing modeling error of graphical methods for estimating volume of distribution measurements in PIB-PET study

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