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Evaluation of D-isomers of O-18F-fluoromethyl, O-18F-fluoroethyl and O-18F-fluoropropyl tyrosine as tumour imaging agents in mice

  • Molecular imaging
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

The aim of this study was to evaluate the properties of the D-amino acid isomers O-18F-fluoromethyl tyrosine (18F-FMT), O-18F-fluoroethyl tyrosine (18F-FET) and O-18F-fluoropropyl tyrosine (18F-FPT) as tumour-detecting agents with PET in comparison with the corresponding L-isomers. L- or D-18F-FMT, 18F-FET or 18F-FPT, prepared by 18F-fluoromethylation, 18F-fluoroethylation or 18F-fluoropropylation of L- and D-tyrosine, was intravenously injected into BALB/cA Jcl-nu mice bearing HeLa tumour cells. At 5, 15, 30 and 60 min post intravenous administration, the uptake of each compound in normal abdominal organs and xenotransplanted HeLa cells was determined using the tissue dissection method. Metabolic stability analyses of these compounds in the plasma were performed with the thin-layer chromatography method. In the plasma fraction, although L- and D-isomers of 18F-FMT, 18F-FET and 18F-FPT provided comparable metabolic stability, D-isomers of these labelled compounds revealed a faster elimination rate than their L-isomers, with a higher peak uptake in the blood and kidney 5 min post administration. Compared with natural amino acid ligands, such as L-11C-methionine, the uptake of L-isomers of these labelled compounds was relatively low and stable in the abdominal organs, while D-isomers revealed much lower and faster clearance rates compared with the corresponding L-isomers. Among the abdominal organs, the pancreas showed relatively high uptake of all the labelled compounds used here, and the uptake of D-isomers was much lower than that of the L-isomers. Although tumour uptake levels of D-isomers of 18F-FMT, 18F-FET and 18F-FPT were almost 95%, 43% and 39% of the uptake levels of each of the L-isomers 60 min post administration, the tumour-to-blood ratios of these D-isomers were 181%, 137% and 101% of the ratios of the corresponding L-isomers. D-isomers of 18F-FMT and 18F-FET indicated improved tumour-to-liver ratios compared with the corresponding L-isomers, and D-18F-FPT showed the highest tumour-to-pancreas ratio among all the other compounds assayed here. These results suggest that D-isomers of 18F-fluoroalkyl tyrosine analogues are potential tracers for tumour imaging with PET.

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Acknowledgements

We gratefully acknowledge the excellent technical assistance provided by Shingo Nishiyama and Norihiro Harada in the synthesis of the labelled compounds. This study was supported in part by Research and Development of Technology for Measuring Vital Function Merged with Optical Technology, Research and Development Project Aimed at Economic Revitalisation.

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  1. PET Center, Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamamatsu,, Shizuoka, 434-8601, Japan

    Hideo Tsukada, Kengo Sato, Dai Fukumoto & Takeharu Kakiuchi

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  1. Hideo Tsukada
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  2. Kengo Sato
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  3. Dai Fukumoto
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  4. Takeharu Kakiuchi
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Correspondence to Hideo Tsukada.

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Tsukada, H., Sato, K., Fukumoto, D. et al. Evaluation of D-isomers of O-18F-fluoromethyl, O-18F-fluoroethyl and O-18F-fluoropropyl tyrosine as tumour imaging agents in mice. Eur J Nucl Med Mol Imaging 33, 1017–1024 (2006). https://doi.org/10.1007/s00259-006-0076-8

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  • DOI: https://doi.org/10.1007/s00259-006-0076-8

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