Identifiability analysis and parameter identification of an in vivo ligand-receptor model from PET data

The identification of the model parameters from data obtained with a single tracer injection leads to disappointing numerical results, since most of the parameters have to be considered as unidentifiable. A protocol including two injections, a first injection of the labeled ligand and a second injection of the cold ligand (displacement experiment), leads to two very different numerical solutions, which is surprising, since such multiplicity of solutions was not indicated by a preliminary theoretical identifiability study. It is shown that a three-injections protocol, including both a displacement and a coinjection experiment, makes it possible to determine which of these two solutions is biologically valid.