“…Thus, although fluorine is not present in natural amino acids, the longer physical half-life of 18 F and the greatest sterical and electronic similarities to hydrogen (which enable the conservation of bond length, strength, and atomic radius when substituting a C-H or C-OH group for a C-F), made this radioisotope very desirable for the radiolabeling of amino acid derivatives [240][241][242]. The addition of fluorine can, however, modify the lipophilicity, pKa, and the biological properties of natural substrates, especially in small molecules such as L-arginine (Figure 8), since slight structural changes or the addition of prosthetic groups are needed to accommodate 18 Although they were not designed or evaluated to specifically or selectively bind arginase, the 18 F-labeled arginine derivatives reported in the literature showed good potential for PET imaging of the arginine metabolism in tumors [243][244][245], especially if compared with the image pattern theoretically expected for the natural substrate analog [ 13 N/ 11 C]arginine [236]. If cleverly designed, the advantage of using radiolabeled modified amino acids, from a PET-imaging point of view, is that they do not metabolize in the same way as the natural ones [241].…”