Preloading with L-BPA, L-tyrosine and L-DOPA enhances the uptake of [18F]FBPA in human and mouse tumour cell lines

Wingelhofer, Bettina; Kreis, Katharina; Mairinger, Severin; Muchitsch, Viktoria; Stanek, Johann; Wanek, Thomas; Langer, Oliver; Kuntner, Claudia

doi:10.1016/j.apradiso.2016.08.026

Cited by 12 publications

(11 citation statements)

References 25 publications

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“…15 Wingelhofer et al also found that pre-treatment with L-tyrosine enhanced the 18 F-FBPA (2-fluoro-4-borono-L-phenylalanine) intracellular concentration in three different types of human and mouse tumour cell lines. 27 Capuani et al presented two studies showing the possibility of enhancing BPA uptake by using another L-amino acid (L-DOPA) with C6-glioma cells in vitro and in vivo. 28,29 In contrast, Detta and Cruickshank presented a study on human brain tumour and brain around tumour harvested from patients with glioblastoma, which showed that pre-loading with L-tyrosine did not show any improvement in BPA uptake in these tissues.…”

Section: Introductionmentioning

confidence: 99%

Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS

Aldossari

McMahon

Lockyer

et al. 2019

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Section: Introductionmentioning

confidence: 99%

Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS

Aldossari

McMahon

Lockyer

et al. 2019

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“…1C) (5). In line with this possible mechanism, a previous study reported that preadministration of substrates of LAT1 enhanced tumor accumulation of BPA (13), and another study demonstrated that preloading of BPA in cancer cells augmented the cellular uptake of 18 F-BPA (14), indicating that both extracellular and intracellular BPA molecules should be subject to the antiport mechanism of LAT1. Considering these backgrounds, we hypothesized that modulation of subcellular localization of BPA should prevent intracellular BPA from untoward export by the antiport mechanism.…”

Section: Introductionmentioning

confidence: 71%

Poly(vinyl alcohol) boosting therapeutic potential of p -boronophenylalanine in neutron capture therapy by modulating metabolism

et al. 2020

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In the current clinical boron neutron capture therapy (BNCT), p-boronophenylalanine (BPA) has been the most powerful drug owing to its ability to accumulate selectively within cancers through cancer-related amino acid transporters including LAT1. However, the therapeutic success of BPA has been sometimes compromised by its unfavorable efflux from cytosol due to their antiport mechanism. Here, we report that poly(vinyl alcohol) (PVA) can form complexes with BPA through reversible boronate esters in aqueous solution, and the complex termed PVA-BPA can be internalized into cancer cells through LAT1-mediated endocytosis, thereby enhancing cellular uptake and slowing the untoward efflux. In in vivo study, compared with clinically used fructose-BPA complexes, PVA-BPA exhibited efficient tumor accumulation and prolonged tumor retention with quick clearance from bloodstream and normal organs. Ultimately, PVA-BPA showed critically enhanced antitumor activity in BNCT. The facile technique proposed in this study offers an approach for drug delivery focusing on drug metabolism.

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“…For example, in human hepatocellular carcinoma cells, no trans-stimulation effect was seen [27]. Likewise, melanoma cells showed no significantly increased boron content after trans-stimulation, and a lower boron uptake after 90 min of trans-stimulation was observed for adenocarcinoma cells and human hepatocellular carcinoma cells [28]. Most commonly, the concentration of the used L-tryrosine solution was 5 mmol/L, as this concentration is known to be non-toxic in vitro.…”

Section: Discussionmentioning

confidence: 99%

Does Trans-Stimulation of L-Tyrosine Lead to an Increase in Boron Uptake in Head and Neck Squamous Cell Carcinoma Cells?

2021

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(1) Background: For advanced head and neck squamous cell carcinoma (HNSCC), boron neutron capture therapy (BNCT) is a potential therapeutic option, but high concentrations of boron within HNSCC are necessary. Therefore, this in vitro pilot study examined the uptake and concentration of boron in HNSCC cells using the trans-stimulation effect of L-tyrosine when compared to non-stimulated samples. (2) Methods: Two HNSCC cell lines were incubated with L-tyrosine for up to two hours, followed by incubation with three L-para-boronophenylalanine (BPA) concentrations (5, 20, 50 ppm) at eight incubation times (1–4.5 h in half-hour steps). Subsequently, cellular boron uptake was measured via inductively coupled plasma mass spectrometry. (3) Results: No differences between laryngeal and oral SCC cells were seen; therefore, data were pooled. In total, boron uptake was not significantly increased in trans-stimulated samples when compared to the control group (all p > 0.05). Nevertheless, with trans-stimulation, higher BPA concentrations resulted in higher intracellular boron concentrations (5 < 20 < 50 ppm; all: p < 0.05), whereas these differences were less distinct in the non-trans-stimulated group. (4) Conclusions: The effect of trans-stimulation for up to two hours seems to be less relevant for HNSCC, though trans-stimulated HNSCC cells seem to have a more distinct BPA-dose-dependent cellular boron uptake that might be addressed in further research.

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Preloading with L-BPA, L-tyrosine and L-DOPA enhances the uptake of [18F]FBPA in human and mouse tumour cell lines

Cited by 12 publications

References 25 publications

Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS

Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS

Poly(vinyl alcohol) boosting therapeutic potential of p -boronophenylalanine in neutron capture therapy by modulating metabolism

Does Trans-Stimulation of L-Tyrosine Lead to an Increase in Boron Uptake in Head and Neck Squamous Cell Carcinoma Cells?

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