Novel Statistical Model for Determining the Extent of FDG Excretion

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The radiolabelled glucose analogue, 18F-fluoro-deoxyglucose (FDG) is widely used in the diagnosis and staging of cancer. FDG becomes concentrated in cancer cells due to their increased need for glucose and can be visualised using positron emission tomography (PET) imaging. In addition to highlighting the presence and location of a tumour, the intensity of the signal provides an indication of how aggressive and fast-growing it is.

PET scans are conducted in fasting patients so that the signal is not diluted by unlabelled glucose and because other cells generally do not use glucose in the fasting state. However, since it is not practical to conduct numerous PET scans over a long period, only one image is obtained at the point equilibrium is reached. This means that only tracer uptake and not tracer availability can be measured. The latter is usually considered to be relatively similar between patients and is therefore ignored.

FDG renal excretion

Unlike glucose, FDG is excreted in the urine since the modified structure of FDG prevents it being reabsorbed from the kidneys as it cannot be taken up by the glucose transporter proteins in the renal tubules. This results in radioactivity also accumulates in the bladder, which reduces the amount available for tumour identification. Consequently, quantification of FDG renal excretion is important to ensure that the FDG uptake accurately reflects tumour metabolism.

The extent of FDG excretion in the urine can be determined by calculating the average clearance of the tracer from blood in a person without any cancers. This information can be obtained from PET scans, but is not easy to do routinely since it requires simultaneous imaging of several parts of the body at several time points. Furthermore, it does not give detailed information of the local movements of the tracer.

Novel compartmental model for renal excretion

Researchers have now developed a compartmental model and mathematical analysis methodology to derive FDG excretion values from PET data. Based on observations of actual local FDG movements in mice (using a micro-PET system that provides images of an entire mouse) they developed a novel compartmental model. Compartmental analysis is commonly used in physiological PET studies of animal models. However, the latest model differs from traditional renal models in that it comprises three rather than two compartments (parenchyma, pre-urine and urine) so as to take into account the accumulation of FDG prior to excretion.

The movement of FDG between the compartments was mathematically determined using a linear system of ordinary differential equations. Based on physiological processes, it was established that there are six exchange coefficients describing the efficiency of tracer transmission between the different compartments.

ACO analysis for compartmental model reduction

These six unknown exchange coefficients were calculated using an Ant Colony Optimization (ACO) algorithm.

ACO is a complicated technique based on the behaviours of ants to choose the shortest route between a food source and the nest. It uses statistical probabilities to find the optimal path in a changing environment. It has been successfully used to solve a wide range of combinatorial optimization problems and has proved especially effective in compartmental analysis.

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The latest research showed that one of the specific tracer coefficients determined from the compartmental model is strongly correlated to average clearance and that another computed coefficient provides a reliable local description of the effectiveness with which FDG is exchanged between the different physiological compartments. The calculations were repeated using a standard least-squares method, and this showed that the ACO method provided similar average values but with reduced associated uncertainties.

Clinical benefit

This novel computational method for the quantitative assessment of FDG renal excretion process could be particularly useful for studying the effect of drugs that lower blood glucose levels by reducing tubular sugar reabsorption so that excess glucose is excreted in the urine. Since such drugs may well be taken by diabetic patients who need tumour evaluations, they could distort the results obtained from FDG assessment of tumour activity. This newly developed methodology would allow the effects of such drugs to be determined and the level of tumour activity could be adjusted accordingly. Since the prevalence of diabetes is steadily increasing, this will be a valuable tool to ensure standard FDG uptake measurements remain a reliable marker of tumour metabolism.


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Last updated: Mar 6, 2019 at 5:32 AM

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