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

Watabe, Tadashi; Ikeda, Hayato; Nagamori, Shushi; Wiriyasermkul, Pattama; Tanaka, Yôko; Naka, Sadahiro; Kanai, Yasukazu; Hagiwara, Kohei; Aoki, Masanao; Shimosegawa, Eku; Kanai, Yoshikatsu; Hatazawa, Jun

doi:10.1007/s00259-016-3487-1

Cited by 55 publications

(51 citation statements)

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“…A rat glioma C6 cell line, derived from gliomas induced by N -nitrosomethylurea, was provided by the RIKEN BRC (Tsukuba, Japan). Rat xenograft models of C6 glioma were evaluated 3 weeks after the tumor implantation in the subcutaneous region of either side [7]. All animal experiments were performed in compliance with the guidelines of the Institute of Experimental Animal Sciences.…”

Section: Methodsmentioning

confidence: 99%

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Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET

et al. 2017

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PurposeThe purpose of this study was to establish a practical method to estimate the absolute boron concentrations in the tissues based on the standardized uptake values (SUVs) after administration of 4-borono-phenylalanine (BPA) using 4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) PET.MethodsRat xenograft models of C6 glioma (n = 7, body weight 241 ± 28.0 g) were used for the study. PET was performed 60 min after intravenous injection of 18F-FBPA (30.5 ± 0.7 MBq). After the PET scanning, BPA-fructose (167.3 ± 18.65 mg/kg) was administered by slow intravenous injection to the same subjects. The rats were killed 60 min after the BPA injection and tissue samples were collected from the major organs and tumors. The absolute boron concentrations (unit: ppm) in the samples were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The boron concentrations in the tissues/tumors were also estimated from the 18F-FBPA PET images using the following formula: estimated absolute boron concentration (ppm) = 0.0478 × [BPA dose (mg/kg)] × SUV. The measured absolute boron concentrations (mBC) by ICP-OES and the estimated boron concentrations (eBC) from the PET images were compared.ResultsThe percent difference between the mBC and eBC calculated based on the SUVmax was −5.2 ± 21.1% for the blood, −9.4 ± 22.3% for the brain, 1.6 ± 21.3% for the liver, −14.3 ± 16.8% for the spleen, −9.5 ± 27.5% for the pancreas, and 3.4 ± 43.2% for the tumor. Relatively large underestimation was observed for the lung (−48.4 ± 16.2%), small intestine (−37.8 ± 19.3%) and large intestine (−33.9 ± 11.0%), due to the partial volume effect arising from the air or feces contained in these organs. In contrast, relatively large overestimation was observed for the kidney (34.3 ± 29.3%), due to the influence of the high uptake in urine.ConclusionsThe absolute boron concentrations in tissues/tumors can be estimated from the SUVs on 18F-FBPA PET using a practical formula. Caution must be exercised in interpreting the estimated boron concentrations in the lung, small intestine and large intestine, to prevent the adverse effects of overexposure, which could occur due to underestimation by partial volume effect using PET.Electronic supplementary materialThe online version of this article (doi:10.1007/s12149-017-1172-5) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

“…18 F-FBPA was prepared as described previously, using an F-1 synthesizer (Sumitomo Heavy Industries, Tokyo, Japan) [7]. PET/CT data were acquired with a small-animal PET system (Inveon PET/CT system, Siemens Medical Solutions) [8].…”

Section: Methodsmentioning

confidence: 99%

Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET

et al. 2017

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“…In our previous studies, we demonstrated high levels of accumulation of various amino acid PET probes, such as 18 F-FBPA, 18 F-FAMT and 11 C-MET, in Oncotarget 1390 www.oncotarget.com C6 glioma. Moreover, we demonstrated the functional expression of LAT1 in these tumors using histology and western blot analyses [5,15]. A western blot analysis of GL261 cells also revealed strong expression of LAT1 [16].…”

Section: Discussionmentioning

confidence: 69%

“…Oncotarget 1389 www.oncotarget.com emission tomography (PET), such as 11 C-methionine ( 11 C-MET), 18 F-fluorodihydroxyphenylalanine ( 18 F-DOPA), and 18 F-fluoroethyltyrosine ( 18 F-FET), are used mainly to evaluate the extent of tumor invasion and differentiate recurrence from radiation necrosis [3,4]. Additionally, phenylalanine (PA) derivatives such as 18 F-fluoro-borono-PA ( 18 F-FBPA) and 4-borono-L-PA (BPA) specifically target tumors and are used mainly in the context of boron neutron capture therapy [5]. They were both reported to be substrates of the L-type amino acid transporter 1 (LAT1) and were found to be taken up selectively by tumors, with minimal physiological accumulation in normal organs [5,6].…”

Section: Research Papermentioning

confidence: 99%

“…Additionally, phenylalanine (PA) derivatives such as 18 F-fluoro-borono-PA ( 18 F-FBPA) and 4-borono-L-PA (BPA) specifically target tumors and are used mainly in the context of boron neutron capture therapy [5]. They were both reported to be substrates of the L-type amino acid transporter 1 (LAT1) and were found to be taken up selectively by tumors, with minimal physiological accumulation in normal organs [5,6]. The derivative labelled with the gamma emitting isotope, para-123 I-iodo-L-phenylalanine ( 123 I-IPA), has been used with some success as a diagnostic imaging agent in glioblastoma patients [7].…”

Section: Research Papermentioning

confidence: 99%

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Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

et al. 2020

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Phenylalanine derivatives, which target tumors especially through L-type amino acid transporter-1 (LAT1), have elicited considerable attention. In this study, we evaluated the treatment effect of phenylalanine labeled with the alpha emitter astatine ( 211 At-PA) in tumor bearing mice. The C6 glioma, U-87MG, and GL261 cell lines were subjected to a cellular 211 At-PA uptake analysis that included an evaluation of the uptake inhibition by the system L amino acid transporter inhibitor 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). BCH significantly inhibited para-211 At-PA uptake in C6 glioma (12.2 ± 0.8%), U-87MG (27.6 ± 1.1%), and GL261 (12.6 ± 2.0%) cells compared to baseline, suggesting an uptake contribution by system L amino acid transporters. Subsequently, xenograft and allograft models were prepared by subcutaneously injecting C6 glioma (n = 12) or GL-261 cells (n = 12), respectively. C6 glioma mice received three 211 At-PA doses (0.1, 0.5, or 1 MBq, n = 3/dose), while GL261 mice received one high dose (1 MBq, n = 7). 211 At-PA exhibited a tumor growth suppression effect in C6 glioma models in a dose-dependent manner as well as in GL-261 models. This phenylalanine derivative labeled with astatine may be applicable as an alpha therapy that specifically targets system L amino acid transporters.

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

Kashihara,

Mori,

Nakaichi

et al. 2023

Cancer Medicine

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BackgroundThe correlation between L‐type amino acid transporter 1 (LAT1) expression and 4‐borono‐2‐18F‐fluoro‐phenylalanine (18F‐FBPA) accumulation in humans remains unclear. This study aimed to investigate the correlation between LAT1 expression in tumor tissues and 18F‐FBPA accumulation in patients with head and neck cancer who participated in a clinical trial of 18F‐FBPA positron emission tomography (PET).MethodsAltogether, 28 patients with head and neck cancer who participated in a clinical trial of 18F‐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.ResultsWeak 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 18F‐FBPA accumulation and intensity of LAT1 expression, and the intensity of LAT1 expression was a better predictor of treatment response.Conclusion18F‐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.

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

Cited by 55 publications

References 30 publications

Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET

Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

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

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

Cited by 55 publications

References 30 publications

Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET

Practical calculation method to estimate the absolute boron concentration in tissues using 18F-FBPA PET

Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice

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

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