2.3.3. [18F]FGln

[ 18F]FGln, an analog of natural glutamine regulated by several glutamine (Gln) transporters (solute carrier family 1 member 5, SLC1A5; solute carrier family 38 member 1, SLC38A1; and SLC7A5; etc.), has been tested and subsequently considered as a promising probe for assessing glutamine metabolism in tumors [61]. Its use is justified by the understanding that tumor cells need extra nutrition and energy for rapid growth and proliferation, while glutamine metabolism is occasionally used by the cell as an alternative to glucose [74]. [18F]FGln can further complement the diagnostic capacity of [18F]FDG by detecting Gln metabolic changes in PTCs [62]. In [18F]FGln imaging, excellent contrast

images can be made only 10 min after injection, while late-phase imaging (60 min) would cause a high background to some extent [62] (Figure 4).

**Figure 4.** Example of a PTC revealed by [18F]FGln at 10 min (**A**) and 60 min (**B**) post-injection, respectively. The arrows indicate the malignant lesion. Reproduced with permission from [62], copyright 2020 Springer Nature Inc.

[ 18F]FAMT, [18F]FET, and the newly reported [18F]NKO-035 are all transported by L-type amino acid transporters, which are overexpressed in tumor cells [21,75]. However, data for those probes remain inadequate now. Furthermore, unlike other amino acid tracers transported by multiple unspecific amino acid transporters, [18F]FAMT has an α-methyl moiety that allows it to be exclusively specific to SLC7A5, making it highly tumor-specific [76,77]. Furthermore, [18F]FAMT is more specific for tumors than [18F]FDG, although their sensitivities are similar. However, [18F]FAMT imaging is comparable to [ 18F]FDG imaging in diagnosing tumors other than TCs [20]. Future studies are warranted to investigate the amino acid metabolism in TCs and the diagnostic value of amino acid tracers in large cohorts.
