title: Further evaluation of quantum chemical methods for the prediction of non-specific binding of positron emission tomography tracers.
abstract: The non-specific binding of candidate positron emission tomography (PET) radiotracers causes resulting PET images to have poor contrast and is a key determinant for the success or failure of imaging drugs. Non-specific binding is thought to arise when radiotracers bind to cell membranes and moieties other than their intended target. Our previous preliminary work has proposed the use of the drug-lipid interaction energy descriptor to predict the level of non-specific binding in vivo using a limited set of ten well known PET radiotracers with kinetic modelling data taken from the literature. This work validates and extends the use of the drug-lipid interaction energy descriptor using a new set of twenty-two candidate PET radiotracers with non-specific binding data recently collected at the same imaging centre with consistent methodology. As with the previous set of radiotracers, a significant correlation is found between the quantum chemical drug-lipid interaction energy and in vivo non-specific binding experimental values. In an effort to speed up the calculation process, several semi-empirical quantum chemical methods were assessed for their ability to reproduce the ab initio results. However no single semi-empirical method was found to consistently reproduce the level of correlation achieved with ab initio quantum chemical methods.
authors: Department of Chemistry and Institute of Chemical Biology, Imperial College London, South Kensington, SW7 2AZ, United Kingdom.
authors: Callum J
authors: CJ
authors: Dickson
authors: Antony D
authors: AD
authors: Gee
authors: Idriss
authors: I
authors: Bennacef
authors: Ian R
authors: IR
authors: Gould
authors: Lula
authors: L
authors: Rosso
mesh_terms: D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D049268:Positron-Emission Tomography; D011789:Quantum Theory; D019275:Radiopharmaceuticals / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008055:Lipids; D019275:Radiopharmaceuticals