Abstract
A recent result obtained by means of an in vitro experiment with cancer cultured cells has configured the endoplasmic reticulum as the preferential site for the accumulation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Such a result is coherent with cell biochemistry and is made more significant by the fact that the reticular accumulation rate of FDG is dependent upon extracellular glucose availability. The objective of the present paper is to confirm in vivo the result obtained in vitro concerning the crucial role played by the endoplasmic reticulum in FDG cancer metabolism. This study utilizes data acquired by means of a Positron Emission Tomography scanner for small animals in the case of CT26 models of cancer tissues. The recorded concentration images are interpreted within the framework of a three-compartment model for FDG kinetics, which explicitly assumes that the endoplasmic reticulum is the dephosphorylation site for FDG in cancer cells. The numerical reduction of the compartmental model is performed by means of a regularized Gauss-Newton algorithm for numerical optimization. This analysis shows that the proposed three-compartment model equals the performance of a standard Sokoloff's two-compartment system in fitting the data. However, it provides estimates of some of the parameters, such as the phosphorylation rate of FDG, more consistent with prior biochemical information. These results are made more solid from a computational viewpoint by proving the identifiability and by performing a sensitivity analysis of the proposed compartment model.
Highlights
We proved that the proposed model is identifiable, but a preliminary sensitivity analysis clearly showed that the sensitivity of k5 and k6, i.e. of the input rate of FDG6P into endoplasmic reticulum (ER) and of its rate of dephosphorylation, is low, so that the determination of these crucial kinetic parameters by the given experimental data may be affected by
This paper has shown that an accumulation of FDG in phosphorylated form in ER is compatible with FDG Positron Emission Tomography (FDG-PET) data recorded from animal models of CT26
This result has been achieved by introducing a novel compartment model where the two available compartments for phosphorylated tracer, cytosolic and ER-localized, were treated on the same level, with no a priori constraints imposed to the model
Summary
The objective of the present paper is to confirm in vivo the result obtained in vitro concerning the crucial role played by the endoplasmic reticulum in FDG cancer metabolism. The main objective of the present paper is to discuss the reliability of the proposed threecompartment model for the analysis of FDG kinetics in tissues in vivo
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