A fluorine-18 labeled radiotracer for PET imaging of γ-glutamyltranspeptidase in living subjects

Abstract

A radiotracer ([18F]GCPA)2 for sensitively and specifically detecting the expression level of γ-glutamyltranspeptidase in living subjects was reported.

Optimized molecular design of PET probe for the visualization of γ-glutamyltranspeptidase activity in tumors

“…4d shows that the tumor/muscle uptake ratio in the U87 model was 4.15 AE 0.37 at 10 min post injection and 4.21 AE 0.37 at 60 min, which was approximately 2.5 times that in NCI-H1299 tumor-bearing mice (1.63 AE 0.11 at 10 min and 1.77 AE 0.08 at 60 min post injection). They were also higher than those of [ 18 F]1G (o2 within 60 min) and ([ 18 F]GCPA) 2 (2.56 AE 0.19 at 10 min and 2.15 AE 0.06 at 30 min post injection), 25,26 confirming the more prominent targeting specificity of [ 18 F]JM-10. To further demonstrate the targeting specificity of the tracer [ 18 F]JM-10 for GGT, a blocking experiment was also carried out in the U87 tumor-bearing mice pretreated with a GGT enzyme inhibitor (GGsTop).…”

“…According to the PET imaging results, the radioactivity of the probe in the abdomen accumulated significantly over time. On the one hand, this may be attributed to the strong lipophilicity of [ 18 F]JM-10, whose log P value is significantly higher than that of the probe ([ 18 F]GCPA) 2 (À1.02 AE 0.04 vs. À1.66 AE 0.02), 26 and previous studies have shown that lipophilicity is positively correlated with liver uptake. 34 On the other hand, since GGT is widely distributed in the liver, kidneys and pancreas, the probes targeting GGT tend to show high uptake in these organs.…”

“…4b), the tumor uptake value was 4.98 AE 0.83% ID mL À1 at 5 min post injection and reached a maximum value of 8.24 AE This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2022 0.87% ID mL À1 at 15 min, which was 2.58-fold that of [ 18 F]1G (3.20 AE 0.29% ID mL À1 ) and 1.76-fold that of ([ 18 F]GCPA) 2 (4.66 AE 0.79% ID mL À1 ). 25,26 This might be attributed to the following reasons: U87 cells naturally possess a higher expression level of GGT than HCT116 cells, the introduction of glycine enhances the flexibility of the skeleton, 36 and the optimization of ethyl disulfide bond reduces the resistance to GSH, thus promoting the in situ intermolecular condensation process. The formed dimers and nanoparticles with strong hydrophobicity and large size effectively enhanced the retention of the probe in tumor cells.…”

“…23,24 Up to now, PET imaging probes for monitoring GGT activity in vivo have rarely been reported. 25,26 Recently, the first GGT-controlled PET probe [ 18 F]1G was reported by our group to visualize the distribution of GGT in living subjects. 25 When the probe entered tumor cells, it could form more rigid and hydrophobic dimers via a CBT-Cys click condensation reaction and further self-assemble into nanoparticles, which could significantly enhance the imaging contrast and signal-to-noise ratio (S/N).…”

“…23,24 Up to now, PET imaging probes for monitoring GGT activity in vivo have rarely been reported. 25,26…”