Biological evaluation of new [18F]F-labeled synthetic amino acid derivatives as an oncologic radiotracer

Objectives This study aimed to examine the tumoral uptake of new amino acid positron emission tomography (PET) tracers, which are (S)-2-amino-3-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)propanoic acid (AMC-101), (S)-2-amino-4-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid (AMC-102) and (S)-2-amino-5-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid (AMC-103), in vivo and in vitro.

Methods In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6. To identify the specific amino acid transporter, 2-aminobicyclo[2,2,1] heptane-2-carboxylate (BCH), 2-(methylamino) isobutyrate (MeAIB) and mixture of L-alanine, L-serine and L-cysteine (ASC) were used in competitive inhibition tests. In vivo dynamic PET images were acquired for two hours using 9L xenograft mouse model after AMC administrations. [18F]FDOPA PET studies, with and without S-carbidopa pretreatment, were done for comparison. Uptake ratios of tumor to muscle (T/M), and tumor to brain (T/B) were also obtained using the mean standardized uptake value (SUV).

Results All three AMCs showed good in vitro cell uptake with AMC-101 showing a higher uptake than AMC-102 and 103. Uptake of AMCs was inhibited by ASC and BCH in a concentration-dependent manner, not by MeAIB. AMCs visualized tumors on PET clearly. Thirty minutes after injection, the mean SUV of the tumor measured as 1.59 ± 0.05, 1.89 ± 0.27 and 1.74 ± 0.13 for AMC-101, 102, and 103, respectively. T/M ratios of AMC-101, 102, and 103 were 3.24 ± 0.40, 2.15 ± 0.18 and 2.96 ± 0.86, 30 minutes after injection. Tumor uptake of [18F]FDOPA was higher than the AMCs; however, the T/M and T/B ratios were smaller than the AMCs, due to increased background activity.

Conclusions AMCs were uptaked in tumor in vitro via the amino acid transporter L and ASC. Also, AMCs were helpful in visualizing tumor uptake with high contrast in a 9L tumor model on PET.