Table 2 Examples of metabolic probes used in different imaging modalities. The table describes the mechanism of action of each probe as well as the targets against which it has been used
From: Molecular imaging of viral pathogenesis and opportunities for the future
Modality | Metabolic pathway | Probes | Target | Mechanism of action |
|---|---|---|---|---|
PET | Glycolysis | 18F(FDG) | Cells with increased glucose metabolism | 18F(FDG) uptake is increased in energetically demanding cells—such as cancer cells145. |
PET | Amino acid metabolism | O-(2-18F-fluoroethyl)-l-tyrosine | Gliomas | Low uptake in healthy tissue, increased in gliomas due to higher rates of protein synthesis and transport into the tissue146,147 |
MRI | Glycolysis | H[1-13C] pyruvate | Increased pyruvate to lactate metabolism | Rapid pyruvate to lactate conversion is a hallmark of aggressive cancer148,149. |
Magnetic resonance spectroscopy (MRI) | Pentose phosphate pathway (PPP) | C13 | Telomerase reverse transcriptase (TERT) | TERT is linked to metabolic reprogramming in various cancers, increasing glucose flux through the PPP150. |
SPECT | Amino acid metabolism | L-3-123I-Iodo-α-methyltyrosine (123I-IMT) is | Increased protein metabolism | Gets taken into tumors due to increased amino acid transport but is not incorporated into proteins151,152. |
SPECT | DNA synthesis | 131I or 124I labeled 2-arabino-fluro-5-iodo-2-deoxyuridine (FIAU) | Proliferating tumors | Nucleosides (or analogs) are phosphorylated by thymidine kinases and then incorporated into nascent DNA. FIAU is a uracil analog and has been used to monitor the proliferation of tumors through its incorporation into DNA152. FIAU can be used with different modalities by changing the attached label—for example, 14C-FIAU is a PET probe153. |
SPECT | Hypoxia | 99mTc-pano | Hypoxic tissues | Nitroimidazoles can act as a marker of hypoxia. This is because they are reduced to reactive products in conditions with little oxygen. These reactive products then become trapped in tissues152. |
BLI | Glucose uptake | bioluminescent glucose uptake probe (BiGluc) | Regions of increased glucose uptake | Bioluminescent glucose probe that is taken up by cells with increased glucose needs. Used in animal models that express luciferase. A caged luciferin phosphine (CLP) is given to the animals, followed by glucose azide (GaZ) and imaging 24 h later. CLP and GaZ interaction releases luciferin that can react with luciferase to produce bioluminescence. As GaZ requires transport into the cell using glucose transporters (GLUT), luminescence will be produced proportionally to the amount of GaZ imported. Therefore, stronger bioluminescent signals will be detected in cells with increased GLUT activity to support their metabolic needs. BiGluc has been used to monitor reactions to GLUT blockers for therapeutic potential and has been considered a radioactivity-free alternative to 18F(FDG)154. |
FLI | Lipid metabolism | boron-dipyrromethene (Bodipy) FL c16 | Cells with increased fatty acid uptake | Palmitate analog to measure fatty acid (FFA) uptake. Increased uptake is linked to cancers such as triple-negative breast cancer and can show dysregulations of lipid metabolism. Increased FFA uptake is also linked to more aggressive tumors155. |
NIR FLI | Lipid metabolism | AlexaFFA | Increased fatty acid metabolism | Consists of Alexa Fluor 647 conjugated to palmitic acid. Increased probe uptake in tissues with increased fatty acid metabolism156. |
