Reston, VA – A breakthrough in medical imaging has emerged as researchers introduce a novel PET radiotracer that can distinguish between diseased and healthy tissues based on fructose metabolism, according to a study published in the March issue of The Journal of Nuclear Medicine. Fructose metabolism, or fructolysis, serves as an indicator for various diseases. By noninvasively mapping fructolysis, physicians can enhance disease detection and initiate treatment at earlier stages.
The human body predominantly relies on glucose as its primary biochemical fuel, fueling essential processes such as tissue function, growth, and repair. Glucose is extensively consumed during inflammation and cancer growth, making it detectable through PET scans. However, evidence suggests that certain disease processes can compel cells to utilize alternative fuels, like fructose, for disease progression. Despite this, an accurate PET imaging dye for measuring fructose metabolism has been lacking.
Dr. Adam Shuhendler, Associate Professor and Canada Research Chair at the University of Ottawa, and scientist at the University of Ottawa Heart Institute, emphasized the fundamental importance of fructolysis in various disorders, leading to the development of methods to noninvasively map fructose metabolism. The research team revisited the design of an imaging dye capable of reliably mapping fructose use.
Prior attempts at generating fructose dyes resulted in non-specific accumulation of the PET imaging signal in bone tissue. In this study, researchers utilized the fructose metabolic pathway to guide modifications to fructose with an imaging label, creating a new dye known as [18F]-4-fluorodeoxyfructose (4FDF). Unlike its predecessors, 4FDF successfully trapped labeled fructose in disease tissues while avoiding accumulation in the bone.
Comparing 4FDF to the clinical standard for glucose mapping, FDG, in a mouse model, researchers observed that 4FDF, like FDG, accumulated in tumor tissue. However, unlike FDG, it did not accumulate in the healthy brain or heart, organs with typically high FDG uptake. When inflammation was induced in the brain and heart, both organs exhibited strong 4FDF signals. Notably, bone uptake was minimized with 4FDF, emphasizing the need for specific tissue mapping in cases where a glucose-to-fructose fuel switch is indicative of heart and brain diseases.
Dr. Shuhendler remarked, “For the first time, fructose metabolism can be mapped sensitively with PET imaging, opening new possibilities for imaging-based diagnoses not possible with FDG.” This innovation widens the scope of diseases that can be more sensitively detected, including stroke, brain metastases, and heart attacks. The precise applications are still under investigation.
The study, titled “It’s a Trap! Aldolase-Prescribed C4 Deoxyradiofluorination Affords Intracellular Trapping and the Tracing of Fructose Metabolism by PET,” includes contributions from researchers Alexia Kirby, Dominic Graf, Mojmír Suchý, Nicholas D. Calvert, Thomas A. Charlton, Robert N. Ben, Christina L. Addison, and Dr. Adam Shuhendler.
