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. 2023 Nov;12(21):20564-20572.
doi: 10.1002/cam4.6635. Epub 2023 Oct 25.

Correlation between L-amino acid transporter 1 expression and 4-borono-2-18 F-fluoro-phenylalanine accumulation in humans

Tairo Kashihara  1   2 , Taisuke Mori  3 , Tetsu Nakaichi  2   4 , Satoshi Nakamura  2   4 , Kimiteru Ito  5 , Hiroaki Kurihara  5   6 , Masahiko Kusumoto  5 , Jun Itami  1   7 , Seiichi Yoshimoto  8 , Hiroshi Igaki  1   2
Affiliations

Correlation between L-amino acid transporter 1 expression and 4-borono-2-18 F-fluoro-phenylalanine accumulation in humans

Tairo Kashihara et al. Cancer Med. 2023 Nov.

Abstract

Background: The correlation between L-type amino acid transporter 1 (LAT1) expression and 4-borono-2-18 F-fluoro-phenylalanine (18 F-FBPA) accumulation in humans remains unclear. This study aimed to investigate the correlation between LAT1 expression in tumor tissues and 18 F-FBPA accumulation in patients with head and neck cancer who participated in a clinical trial of 18 F-FBPA positron emission tomography (PET).

Methods: Altogether, 28 patients with head and neck cancer who participated in a clinical trial of 18 F-FBPA PET at our institution between March 2012 and January 2018 were included. Correlations between standardized uptake values (SUVs); the maximum SUV (SUVmax ), the mean SUV within a 1 cm3 sphere centered at a single point, that is, the SUVmax (SUVpeak ), the minimum SUV (SUVmin ), and the intensity of LAT1 expression (maximum and minimum LAT1 expressions) were investigated.

Results: Weak correlations were identified between SUVmax and LAT1 maximum score, SUVmin and LAT1 maximum score, and SUVmin and LAT1 minimum score (ρ = 0.427, 0.362, and 0.330, respectively). SUVmax and LAT1 minimum score, SUVpeak and LAT1 maximum score, and SUVpeak and LAT1 minimum score demonstrated moderate correlations (ρ = 0.535, 0.556, and 0.661, respectively). Boron neutron capture therapy (BNCT) was performed in 2 of the 4 patients with discrepancies between 18 F-FBPA accumulation and intensity of LAT1 expression, and the intensity of LAT1 expression was a better predictor of treatment response.

Conclusion: 18 F-FBPA accumulation and the intensity of LAT1 expression demonstrated a moderate correlation; however, LAT1 expression may be a better predictor of treatment response of BNCT in patients with discrepancies.

Keywords: 4-borono-2-18F-fluoro-phenylalanine positron emission tomography; L-type amino acid transporter 1; boron neutron capture therapy; boronophenylalanine; neoplasm.

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Conflict of interest statement

Mr. Nakamura reports research funds from Cancer Intelligence Care Systems, Inc. outside the submitted work. Dr. Kusumoto reports honoraria from AstraZeneca K.K., Daiichi‐Sankyo Inc., and Daiichi‐Sankyo Co., Ltd., and research funds from Cannon medical systems outside the submitted work. Dr. Itami reports advisor remuneration from HekaBio and SunnyHealth and research funds from Palette Science. Dr. Yoshimoto reports research funds from CHUGAI PHARMACEUTICAL Co., Ltd. outside the submitted work. Dr. Igaki reports research grant from Elekta K.K., Itochu, and AstraZeneca outside the submitted work. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

FIGURE 1
FIGURE 1
Flowchart of patient inclusion.
FIGURE 2
FIGURE 2
Examples of the L‐type amino acid transporter 1 scoring.
FIGURE 3
FIGURE 3
Immunostained images with L‐type amino acid transporter 1 (LAT1) antibody and 4‐borono‐2‐18F‐fluoro‐phenylalanine (18F‐FBPA) positron emission tomography (PET)/computed tomography (CT) images of the same patients. (A‐1) Maximum and minimum LAT1 expressions were 3. (A‐2) The maximum standardized uptake value (SUVmax) was high (6.78). (B‐1) Maximum and minimum LAT1 expressions were 0. (B‐2) SUVmax was low (2.63). (C) This patient had a discrepancy between the intensity of LAT1 expression and SUV accumulation (Patient A in Table 3). (C‐1) Maximum and minimum LAT1 expressions were 3 and 2, respectively. (C‐2, 3) SUVmax at 10 min after 18F‐FBPA administration was high (5.01, C‐2), but washed out early and remained low at 1 h (2.65, C‐3).
FIGURE 4
FIGURE 4
Correlation between the mean standardized uptake value (SUV) within a 1 cm3 sphere centered at a single point that is the maximum SUV (SUVpeak) and the maximum L‐type amino acid transporter 1 (LAT1) score.
See this image and copyright information in PMC

References

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