2′[18F]-fluoroethylrhodamine B is a promising radiotracer to measure P-glycoprotein function

Trencsényi, György; Kertész, István; Krasznai, Zoltán; Máté, Gábor; Szalóki, Gábor; Judit, P. Szabó; Kárpáti, Levente; Márián, Teréz; Goda, Katalin

doi:10.1016/j.ejps.2015.03.026

Cited by 5 publications

(5 citation statements)

References 45 publications

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“…Membrane fraction of NIH 3T3 mouse fibroblast cells expressing wild-type, E556M and quadruple mutant ABCB1 and their ABCB1-negative counterpart was prepared according to Sarkadi et al [56] with minor modifications previously described in [98]. Cells were harvested by scraping them into ice-cold PBS and washed twice at 300 × g for 5 min.…”

Section: Preparation Of Membranesmentioning

confidence: 99%

Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion

et al. 2020

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Several ABC exporters carry a degenerate nucleotide binding site (NBS) that is unable to hydrolyze ATP at a rate sufficient for sustaining transport activity. A hallmark of a degenerate NBS is the lack of the catalytic glutamate in the Walker B motif in the nucleotide binding domain (NBD). The multidrug resistance transporter ABCB1 (P-glycoprotein) has two canonical NBSs, and mutation of the catalytic glutamate E556 in NBS1 renders ABCB1 transport-incompetent. In contrast, the closely related bile salt export pump ABCB11 (BSEP), which shares 49% sequence identity with ABCB1, naturally contains a methionine in place of the catalytic glutamate. The NBD-NBD interfaces of ABCB1 and ABCB11 differ only in four residues, all within NBS1. Mutation of the catalytic glutamate in ABCB1 results in the occlusion of ATP in NBS1, leading to the arrest of the transport cycle. Here we show that despite the catalytic glutamate mutation (E556M), ABCB1 regains its ATP-dependent transport activity, when three additional diverging residues are also replaced. Molecular dynamics simulations revealed that the rescue of ATPase activity is due to the modified geometry of NBS1, resulting in a weaker interaction with ATP, which allows the quadruple mutant to evade the conformationally locked pre-hydrolytic state to proceed to ATP-driven transport. In summary, we show that ABCB1 can be transformed into an active transporter with only one functional catalytic site by preventing the formation of the ATP-locked pre-hydrolytic state in the non-canonical site.

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Section: Preparation Of Membranesmentioning

confidence: 99%

Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion

et al. 2020

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“…It was reported that the MDR had positive expression in MDA-MB-231 and MCF-7 breast cancer cells [ 25 ]. Because some cations are the substrate for MDR protein, cationic radiotracers have been clinically used for noninvasive monitoring of the multidrug resistance transport function in tumors [ 26 , 27 ]. Lissamine Rhodamine B (LRB) is a member of rhodamine derivatives, which is also the substrate for MDR protein.…”

Section: Discussionmentioning

confidence: 99%

The Synthesis and Evaluations of the⁶⁸Ga-Lissamine Rhodamine B (LRB) as a New Radiotracer for Imaging Tumors by Positron Emission Tomography

Yin

et al. 2016

BioMed Research International

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Purpose. The aim of this study is to synthesize and evaluate 68Ga-labeled Lissamine Rhodamine B (LRB) as a new radiotracer for imaging MDA-MB-231 and MCF-7 cells induced tumor mice by positron emission tomography (PET). Methods. Firstly, we performed the radio synthesis and microPET imaging of 68Ga(DOTA-LRB) in athymic nude mice bearing MDA-MB-231 and MCF-7 human breast cancer xenografts. Additionally, the evaluations of 18F-fluorodeoxyglucose (FDG), as a glucose metabolism radiotracer for imaging tumors in the same xenografts, have been conducted as a comparison. Results. The radiochemical purity of 68Ga(DOTA-LRB) was >95%. MicroPET dynamic imaging revealed that the uptake of 68Ga(DOTA-LRB) was mainly in normal organs, such as kidney, heart, liver, and brain and mainly excreted from kidney. The MDA-MB-231 and MCF-7 tumors were not clearly visible in PET images at 5, 15, 30, 40, 50, and 60 min after injection of 68Ga(DOTA-LRB). The tumor uptake values of 18F-FDG were 3.79 ± 0.57 and 1.93 ± 0.48%ID/g in MDA-MB-231 and MCF-7 tumor xenografts, respectively. Conclusions. 68Ga(DOTA-LRB) can be easily synthesized with high radiochemical purity and stability; however, it may be not an ideal PET radiotracer for imaging of MDR-positive tumors.

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“…A description of the design of the fluoride-drying module is illustrated below: 6). [20][21][22][23] As a base for the module, a 2 mm thick aluminum plate was used, which is partially reinforced on the outside with aluminum profiles. The framework and nonelectronic components of the control unit were 3D printed (Figure 4).…”

Section: Automated 18 F-drying Modulementioning

confidence: 99%

“…Fluoroalkylation examples of different PET‐Tracer, 19 2‐[ 18 F]fluoroethyl harmol as monoamino oxidase tracer ( 3 ), 2′[ 18 F]‐fluoroethylrhodamine B as P‐glycoprotein tracer ( 4 ), [ 18 F]FP‐TZTP as muscarinic tracer ( 5 ), [ 18 F]FE‐β‐CIT as dopamine transport tracer ( 6 ) 20–23 …”

Section: Introductionmentioning

confidence: 99%

Open‐source flow setup for rapid and efficient [¹⁸F]fluoride drying for automation of PET tracer syntheses

Menzel,

Cotton,

Ziegler

et al. 2023

Labelled Comp Radiopharmac

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One of the key strategies for radiochemical research facilities is the automation of synthesis processes. Unnecessary manual operations increase the radiation exposure of personnel, while simultaneously threatening the reliability of syntheses. We have previously reported an affordable open‐source system comprising 3D‐printed continuous flow reactors, a custom syringe pump, and a pressure regulator that can be used to perform radiofluorinations. In this paper, we address additional essential processes that are needed for radiotracer development and synthesis, with the aim of making laboratory work safer and research more efficient. We have designed and evaluated a fully automated system for rapidly and effectively processing and drying aqueous [18F]fluoride that can be directly connected to the cyclotron. This process relies on triflyl fluoride gas generation and allows nucleophilic [18F]fluoride to be prepared safely in a hotcell within 10 min and an activity recovery of 91.7 ± 1.6% (n = 5). Owing to the need for convenient radiofluorinated prosthetic ligands, we have adapted our continuous flow system to produce [18F]fluoroethyl tosylate (FEOTs) and [18F]fluoroethyl triflate (FEOTf), prosthetic groups that are widely used for late‐stage fluoroethylation of PET tracers. The processes as well as the radiolabeling of different groups are compared and comprehensively discussed. Having a method providing [18F]fluoroethyl tosylate (FEOTs) as well as [18F]fluoroethyl triflate (FEOTf) quickly and highly efficiently is beneficial for radiochemical research.

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2′[18F]-fluoroethylrhodamine B is a promising radiotracer to measure P-glycoprotein function

Cited by 5 publications

References 45 publications

Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion

Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion

The Synthesis and Evaluations of the⁶⁸Ga-Lissamine Rhodamine B (LRB) as a New Radiotracer for Imaging Tumors by Positron Emission Tomography

Open‐source flow setup for rapid and efficient [¹⁸F]fluoride drying for automation of PET tracer syntheses

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2′[18F]-fluoroethylrhodamine B is a promising radiotracer to measure P-glycoprotein function

Cited by 5 publications

References 45 publications

Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion

Human ABCB1 with an ABCB11-like degenerate nucleotide binding site maintains transport activity by avoiding nucleotide occlusion

The Synthesis and Evaluations of the68Ga-Lissamine Rhodamine B (LRB) as a New Radiotracer for Imaging Tumors by Positron Emission Tomography

Open‐source flow setup for rapid and efficient [18F]fluoride drying for automation of PET tracer syntheses

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The Synthesis and Evaluations of the⁶⁸Ga-Lissamine Rhodamine B (LRB) as a New Radiotracer for Imaging Tumors by Positron Emission Tomography

Open‐source flow setup for rapid and efficient [¹⁸F]fluoride drying for automation of PET tracer syntheses