title: Biological evaluation of new [(18) F]F-labeled synthetic amino acid derivatives as oncologic radiotracers.
abstract: The present study evaluated the tumoral uptake of the novel synthetic amino acid positron emission tomography (PET) tracers (S)-2-amino-3-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)propanoic acid (AMC-101), (S)-2-amino-4-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid (AMC-102), and (S)-2-amino-5-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid (AMC-103), all of which are (S)-2-amino-(4-([(18) F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids. In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6. In vitro competitive inhibition tests were performed to identify the involvement of specific amino acid transporters. In vivo dynamic PET images of 9L xenograft tumor-bearing model mice were acquired over 2 h after AMC administration. [(18) F]FDOPA PET studies were performed with and without S-carbidopa pretreatment for comparison. All three AMCs exhibited good in vitro cell uptake through the L and alanine-serine-cysteine transporters and enabled clear tumor visualization on PET, leaving the brain devoid of the tracer. Thirty minutes after injection, the mean tumor standardized uptake values were 1.59 ± 0.05, 1.89 ± 0.27, and 1.74 ± 0.13 for AMC-101, AMC-102, and AMC-103, respectively. Although the tumor uptake values of AMCs were lower than that of [(18) F]FDOPA with S-carbidopa pretreatment, AMCs enabled higher contrast images with lower background activity compared with [(18) F]FDOPA with S-carbidopa pretreatment. Our results indicate the potential uses of these new synthetic amino acids as oncologic radiotracers.
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
authors.forename: Yeseulmi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
authors.forename: Sang Ju
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Hankuk University of Foreign Studies, Yongin, Kyunggi-do, Korea.
authors.forename: Cheol-Min
authors.initials: CM
authors.lastname: Yook
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
authors.forename: Jin-Sook
authors.initials: JS
authors.lastname: Ryu
authors.affiliation: Department of Nuclear Medicine, College of Medicine, Asan Medical Center, University of Ulsan, Seoul, Korea.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D005910:Glioma / Q000000981:diagnostic imaging* / Q000473:pathology; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D051381:Rats
chemical_list: D000596:Amino Acids; D005462:Fluorine Radioisotopes; D011849:Radioactive Tracers
keywords: (S)-2-amino-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids; AMC; amino acid; click chemistry; positron emission tomography (PET); transporter; tumor