Quantitative brain [18F]FDG PET beyond normal blood glucose levels

Introduction SUV measurements from static brain [¹⁸F]FDG PET acquisitions are a commonly used tool in preclinical research, providing a simple alternative for kinetic modelling, which requires complex and time-consuming dynamic acquisitions. However, SUV can be severely affected by the animal handling and preconditioning protocols, primarily by those that may induce changes in blood glucose levels (BGL). Here, we aimed at developing and investigating the feasibility of SUV-based approaches for a wide range of BGL far beyond normal values, and consequently, to develop and validate a new model to generate standardized and reproducible SUV measurements for any BGL.

Material and methods We performed dynamic and static brain [¹⁸F]FDG PET acquisitions in 52 male Sprague-Dawley rats sorted into control (n = 10), non-fasting (n = 14), insulin-induced hypoglycemia (n = 12) and glucagon-induced hyperglycemia (n = 16) groups. Brain [¹⁸F]FDG PET images were cropped, aligned and co-registered to a standard template to calculate whole-brain and regional SUV. Cerebral Metabolic Rate of Glucose (CMRglc) was also estimated from 2-Tissue Compartment Model (2TCM) and Patlak plot for validation purposes.

Results Our results showed that BGL=100±6 mg/dL can be considered a reproducible reference value for normoglycemia. Furthermore, we successfully established a 2nd-degree polynomial model (C₁=0.66E-4, C₂=-0.0408 and C₃=7.298) relying exclusively on BGL measures at pre-[¹⁸F]FDG injection time, that characterizes more precisely the relationship between SUV and BGL for a wide range of BGL values (from 10 to 338 mg/dL). We confirmed the ability of this model to generate corrected SUV estimations that are highly correlated to CMRglc estimations (R²= 0.54 2TCM CMRgluc and R²= 0.49 Patlak CMRgluc). Besides, slight regional differences in SUV were found in animals from extreme BGL groups, showing that [¹⁸F]FDG uptake is mostly directed toward central regions of the brain when BGLs are significantly decreased.

Conclusion Our study successfully established a non-linear model that relies exclusively on pre-scan BGL measurements to characterize the relationship between [¹⁸F]FDG SUV and BGL. The extensive validation confirmed its ability to generate SUV-based surrogates of CMRglu along a wide range of BGL and it holds the potential to be adopted as a standard protocol by the preclinical neuroimaging community using brain [¹⁸F]FDG PET imaging.