Enhanced tumor retention of the novel LAT1-targeting PET probe [¹⁸F]FAMT-OMe: A comparative study with [¹⁸F]FAMT in...

[¹⁸F]fluoro-L-α-methyltyrosine ([¹⁸F]FAMT) 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, [¹⁸F]FAMT 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, [¹⁸F]FAMT-OMe, and compare its performance with [¹⁸F]FAMT in glioma xenograft mice.

[¹⁸F]-FAMT-OMe was synthesized via nucleophilic substitution. The uptake of [¹⁸F]FAMT-OMe and [¹⁸F]FAMT 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 [¹⁸F]FAMT-OMe or [¹⁸F]FAMT. 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 [¹⁸F]FAMT-OMe compared with [¹⁸F]FAMT in both C6 and U-87MG cells. PET imaging demonstrated significantly greater tumor retention of [¹⁸F]FAMT-OMe than [¹⁸F]FAMT (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 [¹⁸F]FAMT-OMe than [¹⁸F]FAMT (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 [¹⁸F]FAMT-OMe was significantly increased (SUVmean 1.78 ± 0.85 vs. 1.20 ± 0.82, P < 0.05).

[¹⁸F]FAMT-OMe showed improved tumor retention on PET compared with [¹⁸F]FAMT in the C6 glioma tumor model, suggesting its potential utility for future applications in LAT1-targeted PET.