Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2

Masanao Aoki, Tadashi Watabe, Shushi Nagamori, Sadahiro Naka, Hayato Ikeda, Pornparn Kongpracha, Genki Horitsugi, Yasukazu Kanai, Eku Shimosegawa, Yoshikatsu Kanai, Jun Hatazawa

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Abstract

Objective: L-type amino acid transporter 1 (LAT1) is strongly expressed on the cell membrane in various types of human cancer cells, while being minimally expressed in normal or inflammatory tissues. Therefore, LAT1-targeting PET tracers have been developed for cancer-specific imaging. The purpose of this study was to study the distribution of two LAT1-targeting PET tracers, L-4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) and L-3-18F-alpha-methyl tyrosine (18F-FAMT), in relation to the tumor blood flow, using rat xenograft models. Methods: Rat tumor xenograft models of C6 glioma (n = 4; tumors = 8) and MIA PaCa-2 (pancreatic cancer) (n = 4; tumors = 6) were used. The expressions of LAT1 and CD98hc were evaluated by both immunofluorescence staining and western blot analysis. Dynamic PET was performed after injection of 18F-FAMT or 18F-FBPA (scan duration = 70 min) following 15O-water PET (scan duration = 10 min). The PET data were subjected to kinetic analyses, and the K1, k2, and total distribution volume (Vt) were calculated using the one-tissue compartment model. The accumulation of the LAT1 tracers was expressed in terms of their Vt. Tumor blood flow (TBF) was represented by the K1 value in 15O-water PET. Results: LAT1/CD98hc expression was confirmed in both xenografts by immunofluorescence staining. Western blot analysis showed higher functional expression of LAT1 in the C6 glioma cells as compared to the MIA PaCa-2 cells (C6 glioma/MIA PaCa-2 relative expression ratio = 1.70). The Vt values of both 18F-FBPA and 18F-FAMT were significantly higher in the C6 glioma xenografts than in the MIA PaCa-2 xenografts (C6 glioma: 2.27 ± 0.35 and 2.03 ± 0.23, respectively; MIA PaCa-2: 1.28 ± 0.26 and 1.35 ± 0.15, respectively). Meanwhile, there was no significant correlation of the Vt value of either 18F-FBPA or 18F-FAMT with the TBF, in either the C6 glioma or the MIA PaCa-2 xenografts. Conclusions: This study revealed that total distribution volumes of the LAT1-targeting PET tracers 18F-FBPA and 18F-FAMT were independent of the tumor blood flow and might reflect the functional expression levels of LAT1 in the C6 glioma and MIA PaCa-2 xenograft models.

Original languageEnglish
Pages (from-to)394-403
Number of pages10
JournalAnnals of Nuclear Medicine
Volume33
Issue number6
DOIs
Publication statusPublished - 2019 Jun 5

Keywords

  • C6 glioma
  • LAT1
  • MIA PaCa-2
  • Small-animal PET
  • Tumoral blood flow

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Aoki, M., Watabe, T., Nagamori, S., Naka, S., Ikeda, H., Kongpracha, P., Horitsugi, G., Kanai, Y., Shimosegawa, E., Kanai, Y., & Hatazawa, J. (2019). Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-2. Annals of Nuclear Medicine, 33(6), 394-403. https://doi.org/10.1007/s12149-019-01346-9