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Biological evaluation of 3-[18F]fluoro-α-methyl-d-tyrosine (d-[18F]FAMT) as a novel amino acid tracer for positron emission tomography

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Abstract

Objective

3-[18F]Fluoro-α-methyl-l-tyrosine (l-[18F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. Because d-amino acids are not well distributed in non-target organs and are rapidly excreted in urine, the d-isomer of [18F]FAMT could allow clear PET imaging of tumors early after administration. In this study, we prepared 3-[18F]fluoro-α-methyl-d-tyrosine (d-[18F]FAMT) and evaluated its usefulness.

Methods

d-[18F]FAMT was synthesized according to the method for preparation of l-[18F]FAMT. The in vitro and in vivo stability of [18F]FAMT were evaluated by high-performance liquid chromatography. Cellular uptake of [18F]FAMT was evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in LS180 tumor-bearing mice, and the tumors were imaged using a small-animal PET scanner.

Results

The radiolabeling yield of d-[18F]FAMT was approximately 10 %, similar to that of l-[18F]FAMT. Over 95 % of d-[18F]FAMT remained intact in mice until 60 min after administration. d-[18F]FAMT was gradually taken up by the LS180 cells. Tumor uptake of d-[18F]FAMT was competitively inhibited by pretreatment with α-methyl-l-tyrosine, a selective substrate for the system l-amino acid transporter 1 (LAT1), suggesting the involvement of LAT1 in tumor uptake of d-[18F]FAMT. In biodistribution studies, d-[18F]FAMT showed rapid clearance from the blood, marked accumulation and retention in the tumor, and lower accumulation in non-target organs, especially kidney and pancreas, compared to l-[18F]FAMT. The amount of d-[18F]FAMT in the tumor was also reduced, and tumor-to-blood ratio and tumor-to-muscle ratio of d-[18F]FAMT were similar to those of l-[18F]FAMT at every time point. PET imaging with d-[18F]FAMT did not provide a clear image of the tumor early after administration. However, d-[18F]FAMT provided higher tumor-to-background contrast than l-[18F]FAMT.

Conclusions

d-[18F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective imaging compared with l-[18F]FAMT. Thus, d-[18F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.

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Acknowledgments

This work was supported by Funding Program for Next Generation World-Leading Researchers (NEXT program) from Cabinet Office, Government of Japan. We are grateful to Mr. Takashi OGASAWARA for operation of the biomedical cyclotron. We also would like to thank the staff of the Medical Radioisotope Application Group at the Japan Atomic Energy Agency as well as the Departments of Diagnostic Radiology and Nuclear Medicine at Gunma University Graduate School of Medicine for their cooperation and helpful input.

Author information

Authors and Affiliations

  1. Medical Radioisotope Application Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma, 370-1292, Japan

    Yasuhiro Ohshima & Noriko S. Ishioka

  2. Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana, Chuo-ku, Chiba, 260-8675, Japan

    Hirofumi Hanaoka

  3. Department of Molecular Imaging, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Hideyuki Tominaga

  4. Division of Bio-system Pharmacology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan

    Yoshikatsu Kanai & Shushi Nagamori

  5. Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Kyoichi Kaira

  6. Department of Bioimaging Information Analysis, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Aiko Yamaguchi

  7. Department of Diagnostic Radiology and Nuclear Medicine, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi, Gunma, 371-8511, Japan

    Noboru Oriuchi, Yoshito Tsushima & Keigo Endo

Authors
  1. Yasuhiro Ohshima
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  2. Hirofumi Hanaoka
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  3. Hideyuki Tominaga
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  4. Yoshikatsu Kanai
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  6. Aiko Yamaguchi
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  8. Noboru Oriuchi
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  9. Yoshito Tsushima
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  10. Keigo Endo
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  11. Noriko S. Ishioka
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Correspondence to Yasuhiro Ohshima.

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Ohshima, Y., Hanaoka, H., Tominaga, H. et al. Biological evaluation of 3-[18F]fluoro-α-methyl-d-tyrosine (d-[18F]FAMT) as a novel amino acid tracer for positron emission tomography. Ann Nucl Med 27, 314–324 (2013). https://doi.org/10.1007/s12149-013-0687-7

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  • DOI: https://doi.org/10.1007/s12149-013-0687-7

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