Synthesis and characterization of boron fenbufen and its F-18 labeled homolog for boron neutron capture therapy of COX-2 overexpressed cholangiocarcinoma

Yeh, Chun‐Nan; Chang, Chun Ju; Chung, Y.; Tien, Shi-Wei; Chen, Te Fu; Chen, Tsung-Wen; Huang, Ya-Ling; Wang, Hsin‐Ell; Chou, You-Cheng; Chen, Ming-Huang; Chiang, Kun‐Chun; Huang, Wen‐Sheng; Yu, Chung‐Shan

doi:10.1016/j.ejps.2017.07.019

Cited by 11 publications

(7 citation statements)

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“…Hence, a nonpolar liquid phase and a polar solid support, for example, silica cartridge, were employed to redistribute the polar tagged ligand–COX molecule and the nonpolar ligand ( Figure 4 ). 32 Through the nonlinear regression fit, the IC 50 values of ortho -[ 18 F]F- 1 were determined to be 39.0 and 24.5 nM for COX-1 and COX-2, respectively. Our results showed a relatively inferior COX-2 selectivity (1.63) compared with the data from other groups.…”

Section: Resultsmentioning

confidence: 99%

“…In vivo PET studies of ortho -[ 18 F]F- 1 were performed using TAA-induced CCA rats (n=5 at 37 weeks postadministration) and using normal rats as a control (n=3). 32 , 35 These studies were performed at Taipei VGH. The rats were anesthetized through isoflurane inhalation (Forthane; Abbott Laboratories, Abbott Park, IL, USA) in oxygen (200 mL/min) during the imaging study.…”

Section: Discussionmentioning

confidence: 99%

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Synthesis and evaluation of ortho-[18F]fluorocelecoxib for COX-2 cholangiocarcinoma imaging

Chang

Yeh

Chung

et al. 2018

DDDT

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BackgroundAn 18F-tagged NSAID analog was prepared for use as a probe for COX-2 expression, which is associated with tumor development.MethodsThe in vivo uptake of celecoxib was monitored with ortho-[18F]fluorocelecoxib using positron emission tomography (PET). The binding affinity of ortho-[18F]fluorocelecoxib to COX-1 and COX-2 enzymes were assessed using the competitor celecoxib.ResultsThe IC50 values were 0.039 μM and 0.024 μM, respectively. A selectivity index of 1.63 was obtained (COX-2 vs COX-1). COX-2 overexpressed cholangiocarcinoma (CCA) murine cells took up more ortho-[18F]fluorocelecoxib than that by usual CCA cells from 10 to 60 minutes post incubation. Competitive inhibition (blocking) of the tracer uptake of ortho-[18F]fluorocelecoxib in the presence of celecoxib by the COX-2 overexpressed CCA cells and the usual CCA cells gave the IC50 values of 0.5 μM and 46.5 μM, respectively. Based on the in vitro accumulation data and in vivo metabolism half-life (30 min), PET scanning was performed 30–60 min after the administration of ortho-[18F]fluorocelecoxib through the tail vein. Study of ortho-[18F]F-celecoxib in the CCA rats showed a tumor to normal ratio (T/N) of 1.38±0.23 and uptake dose of 1.14±0.25 (%ID/g).ConclusionThe inferior in vivo blocking results of 1.48±0.20 (T/N) and 1.18±0.22 (%ID/g) suggests that the nonspecificity is associated with the complex role of peroxidase or the binding to carbonic anhydrase.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Synthesis and evaluation of ortho-[18F]fluorocelecoxib for COX-2 cholangiocarcinoma imaging

Chang

Yeh

Chung

et al. 2018

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“…Direct fluorination of the borono compounds is also exemplified by boronofenbufen, a COX-2 inhibitor and a member of the class of nonsteroidal anti-inflammatory drugs (NSAIDs) ( Scheme 5 ) [ 68 ]. Cholangiocarcinoma (CCA) that overexpresses COX-2 is a fatal liver cancer with a very low cure rate.…”

Section: Other Non-glioma-directed Boron Agents For Radiofluorinationmentioning

confidence: 99%

“… Electrophilic radiofluorination of a boronofenbufen for targeting COX-2 overexpressed cholangio carcinoma tumors [ 68 ]. In courtesy of the permission of copyright by the publisher of Elsevier.…”

Section: Figures and Schemesmentioning

confidence: 99%

Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of 18F-Labeled C-F and B-F Linkages

Deng

2023

Pharmaceuticals

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Boron neutron capture therapy (BNCT) is a binary therapeutic technique employing a boron agent to be delivered to the tumor site followed by the irradiation of neutrons. Biofunctional molecules/nanoparticles labeled with F-18 can provide an initial pharmacokinetic profile of patients to guide the subsequent treatment planning procedure of BNCT. Borono phenylalanine (BPA), recognized by the l-type amino acid transporter, can cross the blood-brain barrier and be accumulated in gliomas. The radiofluoro BNCT agents are reviewed by considering (1) less cytotoxicity, (2) diagnosing and therapeutic purposes, (3) aqueous solubility and extraction route, as well as (4), the trifluoroborate effect. A trifluoroborate-containing amino acid such as fluoroboronotyrosine (FBY) represents an example with both functionalities of imaging and therapeutics. Comparing with the insignificant cytotoxicity of clinical BPA with IC50 > 500 μM, FBY also shows minute toxicity with IC50 > 500 μM. [18F]FBY is a potential diagnostic agent for its tumor to normal accumulation (T/N) ratio, which ranges from 2.3 to 24.5 from positron emission tomography, whereas the T/N ratio of FBPA is greater than 2.5. Additionally, in serving as a BNCT therapeutic agent, the boron concentration of FBY accumulated in gliomas remains uncertain. The solubility of 3-BPA is better than that of BPA, as evidenced by the cerebral dose of 3.4%ID/g vs. 2.2%ID/g, respectively. While the extraction route of d-BPA differs from that of BPA, an impressive T/N ratio of 6.9 vs. 1.5 is noted. [18F]FBPA, the most common clinical boron agent, facilitates the application of BPA in clinical BNCT. In addition to [18F]FBY, [18F] trifluoroborated nucleoside analog obtained through 1,3-dipolar cycloaddition shows marked tumoral uptake of 1.5%ID/g. Other examples using electrophilic and nucleophilic fluorination on the boron compounds are also reviewed, including diboronopinacolone phenylalanine and nonsteroidal anti-inflammatory agents.

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“…Yeh et al reported the development of m-[ 18 F]fluorofenbufen ester boronopinacol (m-[ 18 F]FFBPin) for boron neutron capture therapy (BNCT) of aggressive cholangiocarcinoma (CCA) that overexpresses COX-2 enzyme [85]. Electrophilic radiofluorination chemistry of protected fenbufen boronopinacol (FBPin) 44 was accomplished using CH 3 COO[ 18 F]F. This radiofluorination reaction produced two products, the desired product meta-[ 18 F]fluorofenbufen pinacol (m-[ 18 F]FFBPin) and ortho-[ 18 F] fluorofenbufen pinacol (o-[ 18 F]FFBPin), in a radiochemical yield of 8% at a molar activity of 15 MBq/µmol (Figure 14).…”

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Fluorine-18 Labelled Radioligands for PET Imaging of Cyclooxygenase-2

2022

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Molecular imaging probes enable the early and accurate detection of disease-specific biomarkers and facilitate personalized treatment of many chronic diseases, including cancer. Among current clinically used functional imaging modalities, positron emission tomography (PET) plays a significant role in cancer detection and in monitoring the response to therapeutic interventions. Several preclinical and clinical studies have demonstrated the crucial involvement of cyclooxygenase-2 (COX-2) isozyme in cancer development and progression, making COX-2 a promising cancer biomarker. A variety of COX-2-targeting PET radioligands has been developed based on anti-inflammatory drugs and selective COX-2 inhibitors. However, many of those suffer from non-specific binding and insufficient metabolic stability. This article highlights examples of COX-2-targeting PET radioligands labelled with the short-lived positron emitter 18F, including radiosynthesis and PET imaging studies published in the last decade (2012–2021).

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Synthesis and characterization of boron fenbufen and its F-18 labeled homolog for boron neutron capture therapy of COX-2 overexpressed cholangiocarcinoma

Cited by 11 publications

References 56 publications

Synthesis and evaluation of <em>ortho</em>-[<sup>18</sup>F]fluorocelecoxib for COX-2 cholangiocarcinoma imaging

Synthesis and evaluation of <em>ortho</em>-[<sup>18</sup>F]fluorocelecoxib for COX-2 cholangiocarcinoma imaging

Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of 18F-Labeled C-F and B-F Linkages

Fluorine-18 Labelled Radioligands for PET Imaging of Cyclooxygenase-2

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