Graphical method to determine sigmoid ligand binding in vivo at low doses

In this study, a graphical method is presented to detect sigmoidal binding of in vivo data at low nonsaturating doses. The method can also be applied when the overall binding includes nonspecific binding. Irrespective of the mathematical expression describing the saturation curve, it is shown that a sigmoid curve, in contrast to a nonsigmoid, can be converted into a peak-shaped curve by normalizing the ordinate values with the corresponding value of the abscissa. Computer simulations of in vivo ligand binding demonstrate this principle for in vivo data plots. Experimental results are described to illustrate this approach based on in vivo binding of the neuroleptic drug N-methylspiperone in the rat brain. It is concluded that the method is in particular useful for in vivo applications, e.g., positron emission tomography (PET) studies in human, because low doses are required, and specifically bound, nonspecifically bound, and unbound ligand do not need to be determined separately.