18 Ffluoro-L-α-methyltyrosine ( 18 FFAMT) has been reported as a positron-emission tomography (PET) probe that has high specificity for L-type amino acid transporter 1 (LAT1), which is overexpressed in various malignant tumors. However, 18 FFAMT showed rapid washout from the tumor and high retention in the kidney. This study aimed to develop and evaluate a novel LAT1-targeting PET probe, 18 FFAMT-OMe, and compare its performance with 18 FFAMT in glioma xenograft mice. 18 F-FAMT-OMe was synthesized via nucleophilic substitution. The uptake of 18 FFAMT-OMe and 18 FFAMT was compared in in vitro studies using C6 glioma and U-87MG cells. PET scans were performed on C6 glioma- and U-87MG tumor-bearing mice ( n = 20 each) following intravenous administration of either 18 FFAMT-OMe or 18 FFAMT. After PET/computed tomography (CT) imaging, the organs were weighed and the radioactivity present was measured using a gamma counter. In vitro analyses demonstrated higher uptake of 18 FFAMT-OMe compared with 18 FFAMT in both C6 and U-87MG cells. PET imaging demonstrated significantly greater tumor retention of 18 FFAMT-OMe than 18 FFAMT (SUVmax at 60 min in C6 glioma: 2.13 ± 0.39 vs. 1.09 ± 0.79, P < 0.05). The kidneys and urine showed significantly lower uptake and excretion of 18 FFAMT-OMe than 18 FFAMT (kidney uptake: SUVmean 3.75 ± 0.89 vs. 5.55 ± 2.44, P < 0.05 urine excretion: SUVmean 16.50 ± 7.65 vs. 34.38 ± 8.74, P < 0.05), while blood retention of 18 FFAMT-OMe was significantly increased (SUVmean 1.78 ± 0.85 vs. 1.20 ± 0.82, P < 0.05). 18 FFAMT-OMe showed improved tumor retention on PET compared with 18 FFAMT in the C6 glioma tumor model, suggesting its potential utility for future applications in LAT1-targeted PET.
Sampunta et al. (Sun,) studied this question.