Application of Metabolic Reprogramming to Cancer Imaging and Diagnosis

Abstract

Cellular metabolism governs the signaling that supports physiological mechanisms and homeostasis in an individual, including neuronal transmission, wound healing, and circadian clock manipulation. Various factors have been linked to abnormal metabolic reprogramming, including gene mutations, epigenetic modifications, altered protein epitopes, and their involvement in the development of disease, including cancer. The presence of multiple distinct hallmarks and the resulting cellular reprogramming process have gradually revealed that these metabolism-related molecules may be able to be used to track or prevent the progression of cancer. Consequently, translational medicines have been developed using metabolic substrates, precursors, and other products depending on their biochemical mechanism of action. It is important to note that these metabolic analogs can also be used for imaging and therapeutic purposes in addition to competing for metabolic functions. In particular, due to their isotopic labeling, these compounds may also be used to localize and visualize tumor cells after uptake. In this review, the current development status, applicability, and limitations of compounds targeting metabolic reprogramming are described, as well as the imaging platforms that are most suitable for each compound and the types of cancer to which they are most appropriate.

Keywords: cancer metabolism; cellular uptake; metabolic reprogramming; molecular imaging.

Figure 1

Available metabolism-based radiotracers and their background. The schematic model shows that monosaccharides (glucose and galactose) and glutamine can be taken up by cells, followed by cascade catalysis and synthesis. Glucosamine, pyruvate, glutamate, acetate, and choline may be intermediates or have further consequences. Furthermore, hypoxia is a metabolic reprogramming event with corresponding detectable targets. The blue color represents the derived radiotracer products.

Figure 2

Available metabolism-based radiotracers and their background. The schematic model shows glycolysis and the further TCA cycle, amino acid biosynthesis. In the path, there are some potential targets with radiotracers (left panel). In addition, the coupling of the folate cycle to the methionine cycle is shown (right panel). The blue color represents the derived radiotracer products.