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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

22.08.2016 | Original Article

¹⁸F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with ¹⁸F-FDG and ¹¹C-Methionine PET

verfasst von: Tadashi Watabe, Hayato Ikeda, Shushi Nagamori, Pattama Wiriyasermkul, Yoko Tanaka, Sadahiro Naka, Yasukazu Kanai, Kohei Hagiwara, Masanao Aoki, Eku Shimosegawa, Yoshikatsu Kanai, Jun Hatazawa

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2017

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Abstract

Purpose

The purpose of this study was to evaluate the usefulness of L-4-borono-2-¹⁸F-fluoro-phenylalanine (¹⁸F-FBPA) as a tumor-specific probe, in comparison to ¹⁸F-FDG and ¹¹C-methionine (Met), focusing on its transport selectivity by L-type amino acid transporter 1 (LAT1), which is highly upregulated in cancers.

Methods

Cellular analyses of FBPA were performed to evaluate the transportablity and K_m value. PET studies were performed in rat xenograft models of C6 glioma (n = 12) and in rat models of turpentine oil-induced subcutaneous inflammation (n = 9). The kinetic parameters and uptake values on static PET images were compared using the one-tissue compartment model (K₁, k₂) and maximum standardized uptake value (SUVmax).

Results

The cellular analyses showed that FBPA had a lower affinity to a normal cell-type transporter LAT2 and induced less efflux through LAT2 among FBPA, Met, and BPA, while the efflux through LAT1 induced by FBPA was similar among the three compounds. The K_m value of ¹⁸F-FBPA for LAT1 (196.8 ± 11.4 μM) was dramatically lower than that for LAT2 (2813.8 ± 574.5 μM), suggesting the higher selectivity of ¹⁸F-FBPA for LAT1. K₁ and k₂ values were significantly smaller in ¹⁸F-FBPA PET (K₁ = 0.04 ± 0.01 ml/ccm/min and k₂ = 0.07 ± 0.01 /min) as compared to ¹¹C-Met PET (0.22 ± 0.09 and 0.52 ± 0.10, respectively) in inflammatory lesions. Static PET analysis based on the SUVmax showed significantly higher accumulation of ¹⁸F-FDG in the tumor and inflammatory lesions (7.2 ± 2.1 and 4.6 ± 0.63, respectively) as compared to both ¹⁸F-FBPA (3.2 ± 0.40 and 1.9 ± 0.19) and ¹¹C-Met (3.4 ± 0.43 and 1.6 ± 0.11). No significant difference was observed between ¹⁸F-FBPA and ¹¹C-Met in the static PET images.

Conclusion

This study shows the utility of ¹⁸F-FBPA as a tumor-specific probe of LAT1 with low accumulation in the inflammatory lesions.

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Titel: 18F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with 18F-FDG and 11C-Methionine PET
verfasst von: Tadashi Watabe
Hayato Ikeda
Shushi Nagamori
Pattama Wiriyasermkul
Yoko Tanaka
Sadahiro Naka
Yasukazu Kanai
Kohei Hagiwara
Masanao Aoki
Eku Shimosegawa
Yoshikatsu Kanai
Jun Hatazawa
Publikationsdatum: 22.08.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2017
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-016-3487-1

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

¹⁸F-FBPA as a tumor-specific probe of L-type amino acid transporter 1 (LAT1): a comparison study with ¹⁸F-FDG and ¹¹C-Methionine PET

Abstract

Purpose

Methods

Results

Conclusion

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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