Design, Synthesis, and Biological Evaluation of a Novel [ 18 F]-Labeled Arginine Derivative for Tumor Imaging.

To better diagnose and treat tumors related to arginine metabolism, (2S,4S)-2-amino-4-(4-(2-(fluoro- 18 F)ethoxy)benzyl)-5-guanidinopentanoic acid ( [ 18 F]7 ) was designed and prepared by introducing [ 18 F]fluoroethoxy benzyl on carbon-4 of arginine. [ 18 F]7 and 7 were successfully prepared using synthesis methods similar to those used for (2S,4S)-4-[ 18 F]FEBGln and (2S,4S)-4-FEBGln, respectively. In vitro experiments on cell transport mechanisms showed that [ 18 F]7 was similar to (2S,4S)4-[ 18 F]FPArg and was transported into tumor cells by cationic amino acid transporters. However, [ 18 F]7 can also enter MCF-7 cells via ASC and ASC2 amino acid transporters. Further microPET-CT imaging showed that the initial uptake and retention properties of [ 18 F]7 in MCF-7 subcutaneous tumors were good (2.29 ± 0.09%ID/g at 2.5 min and 1.71 ± 0.09%ID/g at 60 min after administration), without significant defluorination in vivo. However, compared to (2S,4S)4-[ 18 F]FPArg (3.06 ± 0.59%ID/g at 60 min after administration), [ 18 F]7 exhibited lower tumor uptake and higher nonspecific uptake. When further applied to U87MG imaging, [ 18 F]7 can quickly visualize brain gliomas (tumor-to-brain, 1.85 at 60 min after administration). Therefore, based on the above results, [ 18 F]7 will likely be applied for the diagnosis of arginine nutrition-deficient tumors and efficacy evaluations.