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종양 영상을 위한 신규 아미노산 방사성의약품 (S)-2-amino-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids의 생물학적 평가 : Biological evaluation of (S)-2-amino-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids as oncologic positron emission tomography agent 원문보기

  • 저자

    김예슬미

  • 학위수여기관

    울산대학교

  • 학위구분

    국내석사

  • 학과

    의학과 의과학전공

  • 지도교수

    이종진

  • 발행년도

    2014

  • 총페이지

    30 p.

  • 키워드

    (S)-2-amino-(4-([18F]fluoromethyl)-1H-1 2,3-triazol-1-yl)alkyl acids positron emission tomography (PET) click chemistry tumor; amino acid transporter;

  • 언어

    eng

  • 원문 URL

    http://www.riss.kr/link?id=T13540458&outLink=K  

  • 초록

    Purpose: This study aims to examine the tumoral uptake of new amino acid positron emission tomography (PET) tracers, (S)-2-amino-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids in vivo and in vitro. Methods: Three new amino acid derivatives were synthesized by click chemistry, including (S)-2-amino-3-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)propanoic acid ([18F]AMC-AA-101), (S)-2-amino-4-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)butanoic acid ([18F]AMC-AA-102) and (S)-2-amino-5-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)pentanoic acid ([18F]AMC-AA-103). In vitro cellular uptake was investigated using the rat glioma cell lines 9L and C6 at 10, 60, 120, and 180 minutes after incubation. 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 were used in a competitive inhibition test. In vivo dynamic PET images were acquired for two hours using 9L xenograft mouse model after [18F]AMC-AAs. [18F]FDOPA PETs with and without S-carbidopa treatment were done for comparison. Uptake ratios of tumor to muscle (T/M), and uptake ratios of tumor to brain (T/B) were also obtained using the mean standardized uptake value (SUV). The tumors were extracted and immunohistochemical (IHC) stained using L-type amino acid transporter 1 (LAT1) were performed. Results: All three [18F]AMC-AAs showed good in vitro cell uptake and [18F]AMC-AA-101 showed a higher uptake than [18F]AMC-AA-102 and 103. Uptake of [18F]AMC-AAs was inhibited by ASC and BCH in a concentration-dependent manner. There was no inhibition by MeAIB. [18F]AMC-AAs 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 [18F]AMC-AA -101, 102, and 103, respectively. T/M ratios of [18F]AMC-AA-101, 102, and 103 were 3.24 ± 0.40, 2.15 ± 0.18 and 2.96 ± 0.86 30 minutes after injection, and 3.84 ± 0.03, 2.26 ± 0.09 and 3.20 ± 0.81 after 60 minutes. Brain parenchymal uptake was negligible. [18F]AMC-AAs were excreted mainly via the kidneys. Tumor uptake of [18F]FDOPA was higher than the [18F]AMC-AAs; however, the T/M and T/B ratios were smaller than the [18F]AMC-AAs, due to increased background activity. The mean SUV of the tumor was 2.33 without the S-carbidopa treatment, and 4.44, 30 minutes after an injection of the S-carbidopa treatment. The T/M and T/B ratios of [18F]FDOPA were 2.49 and 1.41, respectively, without S-carbidopa treatment, and 2.01 and 1.53, respectively, 30 minutes after S-carbidopa treatment. Conclusion: (S)-2-amino-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids showed good uptake in vitro via the amino acid transporter L and ASC. Also, (S)-2-amino-(4-([18F]fluoromethyl)-1H-1,2,3-triazol-1-yl)alkyl acids were helpful in visualizing tumor uptake with high contrast in a 9L tumor model.


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