Graphical analysis of reversible radioligand binding from time-activity measurements applied to (N- sup 11 C-methyl)-(-)-cocaine PET studies in human subjects

Journal Article · Sat Sep 01 04:00:00 EDT 1990 · Journal of Cerebral Blood Flow and Metabolism; (USA)

DOI:https://doi.org/10.1038/jcbfm.1990.127· OSTI ID:6528420

Logan, J; Fowler, J S; Volkow, N D; Wolf, A P; Dewey, S L; Schlyer, D J; MacGregor, R R; Hitzemann, R; Bendriem, B; Gatley, S J ^[1]

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1. Brookhaven National Laboratory, Upton, NY (USA)

A graphical method of analysis applicable to ligands that bind reversibly to receptors or enzymes requiring the simultaneous measurement of plasma and tissue radioactivities for multiple times after the injection of a radiolabeled tracer is presented. It is shown that there is a time t after which a plot of integral of t0ROI(t')dt'/ROI(t) versus integral of t0Cp(t')dt'/ROI(t) (where ROI and Cp are functions of time describing the variation of tissue radioactivity and plasma radioactivity, respectively) is linear with a slope that corresponds to the steady-state space of the ligand plus the plasma volume,.Vp. For a two-compartment model, the slope is given by lambda + Vp, where lambda is the partition coefficient and the intercept is -1/(kappa 2(1 + Vp/lambda)). For a three-compartment model, the slope is lambda(1 + Bmax/Kd) + Vp and the intercept is -(1 + Bmax/Kd)/k2 + (koff(1 + Kd/Bmax))-1 (1 + Vp/lambda(1 + Bmax/Kd))-1 (where Bmax represents the concentration of ligand binding sites and Kd the equilibrium dissociation constant of the ligand-binding site complex, koff (k4) the ligand-binding site dissociation constant, and k2 is the transfer constant from tissue to plasma). This graphical method provides the ratio Bmax/Kd from the slope for comparison with in vitro measures of the same parameter. It also provides an easy, rapid method for comparison of the reproducibility of repeated measures in a single subject, for longitudinal or drug intervention protocols, or for comparing experimental results between subjects. Although the linearity of this plot holds when ROI/Cp is constant, it can be shown that, for many systems, linearity is effectively reached some time before this. This analysis has been applied to data from (N-methyl-11C)-(-)-cocaine studies in normal human volunteers and the results are compared to the standard nonlinear least-squares analysis.

• OSTI ID: 6528420
• Journal Information: Journal of Cerebral Blood Flow and Metabolism; (USA), Journal Name: Journal of Cerebral Blood Flow and Metabolism; (USA) Vol. 10:5; ISSN 0271-678X; ISSN JCBMD
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
62 RADIOLOGY AND NUCLEAR MEDICINE
ALKALOIDS
AMINES
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARBON 11
CARBON ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COCAINE
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
DOPAMINE
DRUGS
EMISSION COMPUTED TOMOGRAPHY
EVEN-ODD NUCLEI
HYDROXY COMPOUNDS
ISOTOPES
KINETICS
LEAST SQUARE FIT
LIGANDS
LIGHT NUCLEI
MAMMALS
MAN
MATHEMATICAL MODELS
MAXIMUM-LIKELIHOOD FIT
MEMBRANE PROTEINS
METABOLISM
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
NUMERICAL SOLUTION
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
POSITRON COMPUTED TOMOGRAPHY
PRIMATES
PROTEINS
PSYCHOTROPIC DRUGS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
SYMPATHOMIMETICS
TOMOGRAPHY
VERTEBRATES