Methods for quantification of cerebral glycolytic metabolism using 2-deoxy-2-[18 F]fluoroglucose in small animals

Abstract

The use of the same imaging and quantification techniques in small animals and clinical studies presents the opportunity for direct translational research in drug discovery and development, in neuropharmacological basis of neurological and psychiatric diseases, and in optimization of drug therapy. Thus, positron emission tomography (PET) studies in rodents can bridge the gap between pre-clinical and clinical research. The aim should be to find a method with capability to measure, without compromising accuracy, glucose distribution in the structures of the brain, which can also be used in pathological situations and with applicability for other substances than glucose analogue. Methods: This is a systematic review of several assessment techniques available, including visual and quantitative methods that enable the investigation of the transport mechanisms and enzymes involved in glucose metabolism in the brain. In addition to the ex vivo methods, PET with glucose analogues allows in vivo analyses using qualitative, semiquantitative and quantitative methods. Results: These techniques provide different results, and the applicability of a specific method is related to the purpose of the study and the multiple factors that may interfere in the process. Conclusion: This review provides a solid background of tools and quantification methods for medical physicists and other professionals interested in cerebral glycolytic metabolism quantification in experimental animals. It also addresses the main factors related to animals, equipment and techniques that are used, as well as how these factors should be understood to better interpret the results obtained from experiments.

[18F]FDG/PET: a non-invasive technique for the study of stroke in murine and rat models

“…[ 18 F]FDG/PET studies using mice are not frequent. The reason for this is likely limitations related to the size of the animal's brain, small blood volume for sampling, and cerebral vascular variability between individuals of the same species and lineage [73].…”

“…Values range from 5 to10 mm in equipment for clinical use, and 0.9 mm for devices dedicated to pre-clinical research using fluorine-18 labeled radiopharmaceuticals. Although the absolute values are small, the ratio between resolution and volumes of interest is worse in practice and distortions such as those related to the positron reach before annihilation become more pronounced [73]. Therefore, choosing the most appropriate model for the proposed research and using strategies to homogenize the results are important.…”

Optimization of reconstruction parameters in [18F]FDG PET brain images aiming scan time reduction

“…One of the most commonly used radiotracers, fluorodeoxyglucose labelled with 18 F ([ 18 F]FDG), can provide early signs of neuronal changes (7). FDG is an irreversibly bound tracer that provides direct or indirect measurements of glucose consumption, thus energy production, such as the cerebral metabolic rate of glucose (8). Several studies have reported the possibility of using low activity injection for different PET radiotracers (9)(10)(11)(12)(13)(14).…”