Recent Trends in the Nucleophilic [18F]-radiolabeling Method with No-carrier-added [18F]fluoride

Kim, Dong Wook; Jeong, Hwan Jeong; Lim, Sungjoon; Sohn, Myung‐Hee

doi:10.1007/s13139-009-0008-1

Cited by 21 publications

(32 citation statements)

References 38 publications

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“…Since then, multiple research groups have reported the radiosynthesis of [ 18 F]FLT using this DMTr-Boc-nosyl FLT precursor based on the conventional no-carrier-added radiofluorination method with radiochemical yields ranging from 23-50% (19, 21-24). Particularly, the use of a bulky alcohol as co-solvent in assisting the no-carrier-added radiofluorination is attractive and has been reported to attain [ 18 F]FLT in a high radiochemical yield (60-65%) (25-28). We adapted this high yielding, high selectivity protic solvent chemistry to the EWOD microdevice, and developed a miniature cartridge purification method to eliminate the expensive and complicated HPLC purification.…”

Section: Discussionmentioning

confidence: 99%

Efficient Radiosynthesis of 3′-Deoxy-3′-¹⁸F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip

et al. 2013

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Access to diverse PET tracers for preclinical and clinical research remains a major obstacle to research in cancer and other diseases research. The prohibitive cost and limited availability of tracers could be alleviated by microfluidic radiosynthesis technologies combined with high-yield microscale radiosynthetic method. In this report, we demonstrate the multistep synthesis of 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) with high yield on an electrowetting on dielectric (EWOD) microfluidic radiosynthesizer, previously developed in our group. We have identified and established several parameters that are most critical in the microscale radiosynthesis such as the reaction time, reagent concentration, and molar ratios, to successfully synthesize [18F]FLT in this compact platform. Methods [18F]FLT was synthesized from the 3-N-Boc-1-[5-O-(4,4′-dimethoxytrityl)-3-O-nosyl-2-deoxy-β-d-lyxofuranosyl] thymine precursor on the EWOD chip starting from the first solvent exchange and [18F]fluoride ion activation step to the final deprotection step. The fluorination reaction was performed in a mixture of thexyl alcohol and DMSO. The crude product after deprotection was collected from the chip and purified on a custom-made solid phase extraction (SPE) cartridge and subjected to quality control testing. The purified [18F]FLT was suitable for microPET studies in multiple nude mice xenografted with the A431 carcinoma cell line. Results [18F]FLT was successfully synthesized on the EWOD microdevice coupled with an off-chip SPE purification with a decayed-corrected radiochemical yield of 63±5% (n=5) and passed all of the quality control test required by the United States Pharmacopeia for radiotracers to be injected into humans. We have successfully demonstrated the synthesis of several batches of [18F]FLT on EWOD starting with ∼ 333 MBq of radioactivity and obtained up to 52 MBq (non-decay corrected) of [18F]FLT upon cartridge purification. The specific activity of two representative preparations of [18F]FLT synthesized on the EWOD chip were measured to be 1800 and 2400 GBq/μmol. Conclusion The EWOD microchip and optimized synthesis method in combination represent an effective platform for synthesizing [18F]FLT with high yield and of good quality for imaging. This compact platform, with configurable synthesis steps, could potentially form the basis of a stand-alone system that decouples PET probe production from the cyclotron and specialized radiochemistry facilities and increases diversity and flexibility in probe production.

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Section: Discussionmentioning

confidence: 99%

Efficient Radiosynthesis of 3′-Deoxy-3′-¹⁸F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip

et al. 2013

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“…Labeling at an aryl or heteroaryl carbon is a favored strategy for this purpose. Consequently, the field of PET radiotracer development has sought to develop a battery of methods for unrestricted introduction of [ 18 F]fluoride ion at aryl and heteroaryl groups in late‐stage radiosynthesis . This review specifically covers the growing utility of hypervalent aryliodine compounds as precursors for use in such methods.…”

Section: Introductionmentioning

confidence: 99%

“…The introduction of the aminopolyether, Kryptofix 2.2.2 (K 2.2.2; 4,7,13,16,21,24‐hexaoxa‐1,10‐diazabicyclo[8.8.8]hexacosane), as a phase transfer agent for [ 18 F]fluoride ion by the Jülich group greatly facilitated this advance . Although classical S N Ar reactions with [ 18 F]fluoride ion have led to the development of many successful PET radiotracers, and continue to do so, there are limitations in the substrate scope of this method . Generally, homoarene precursors must contain a good leaving group that is activated by an electron‐withdrawing group in the ortho or para position.…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, the field of PET radiotracer development has sought to develop a battery of methods for unrestricted introduction of [ 18 F]fluoride ion at aryl and heteroaryl groups in late-stage radiosynthesis. [4][5][6][7][8][9] This review specifically covers the growing utility of hypervalent aryliodine compounds as precursors for use in such methods. The coverage is intended to be illustrative rather than exhaustive and builds on a previous review of this area.…”

Section: Introductionmentioning

confidence: 99%

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Hypervalent aryliodine compounds as precursors for radiofluorination

Pike

2018

Labelled Comp Radiopharmac

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Over the last 2 decades or so, hypervalent iodine compounds, such as diaryliodonium salts and aryliodonium ylides, have emerged as useful precursors for labeling homoarenes and heteroarenes with no-carrier-added cyclotron-produced [ F]fluoride ion (t = 109.8 min). They permit rapid and effective radiofluorination at electron-rich as well as electron-deficient aryl rings, and often with unrestricted choice of ring position. Consequently, hypervalent aryliodine compounds have found special utility as precursors to various small-molecule F-labeling synthons and to many radiotracers for biomedical imaging with positron emission tomography. This review summarizes this advance in radiofluorination chemistry, with emphasis on precursor synthesis, radiofluorination mechanism, method scope, and method application.

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“…3,4 Despite the short half-life of fluorine-18 (F-18, t 1/2 = 109.8 min), it is the most popular positron-emitter for PET among various radioisotopes owing to its excellent chemical, physiological and nuclear properties. [3][4][5][6][7] The short half-life of F-18, however, requires rapid, simple and reliable F-18 labeling strategies to obtain new PET molecular imaging probes. 8,9 Because angiogenesis associated with the integrin α v β 3 receptor is a key process in tumor growth and metastasis, PET molecular imaging probes for tumor angiogenesis have potential for early tumor diagnosis and monitoring of the therapeutic effects of various treatments in both pre-clinical and clinical studies.…”

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confidence: 99%

F-18 Labeled RGD Probes Based on Bioorthogonal Strain-Promoted Click Reaction for PET Imaging

Kim

Sachin

Jeong

et al. 2015

ACS Med. Chem. Lett.

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A series of fluorine-substituted monomeric and dimeric cRGD peptide derivatives, such as cRGD-ADIBOT-F (ADIBOT = azadibenzocyclooctatriazole), di-cRGD-ADIBOT-F, cRGD-PEG5-ADIBOT-F, and di-cRGD-PEG5-ADIBOT-F, were prepared by strain-promoted alkyne azide cycloaddition (SPAAC) reaction of the corresponding aza-dibenzocyclooctyne (ADIBO) substituted peptides with a fluorinated azide 3. Among these cRGD derivatives, di-cRGD-PEG5-ADIBOT-F had the highest binding affinity in a competitive binding assay compared to other derivatives and even the original cRGDyk. On the basis of the in vitro study results, di-cRGD-PEG5-ADIBOT-(18)F was prepared from a SPAAC reaction with (18)F-labeled azide and subsequent chemo-orthogonal scavenger-assisted separation without high performance liquid chromatography (HPLC) purification in 92% decay-corrected radiochemical yield (dcRCY) with high specific activity for further in vivo positron emission tomography (PET) imaging study. In vivo PET imaging study and biodistribution data showed that this radiotracer allowed successful visualization of tumors with good tumor-to-background contrast and significantly higher tumor uptake compared to other major organs.

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Recent Trends in the Nucleophilic [18F]-radiolabeling Method with No-carrier-added [18F]fluoride

Cited by 21 publications

References 38 publications

Efficient Radiosynthesis of 3′-Deoxy-3′-¹⁸F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip

Efficient Radiosynthesis of 3′-Deoxy-3′-¹⁸F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip

Hypervalent aryliodine compounds as precursors for radiofluorination

F-18 Labeled RGD Probes Based on Bioorthogonal Strain-Promoted Click Reaction for PET Imaging

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Recent Trends in the Nucleophilic [18F]-radiolabeling Method with No-carrier-added [18F]fluoride

Cited by 21 publications

References 38 publications

Efficient Radiosynthesis of 3′-Deoxy-3′-18F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip

Efficient Radiosynthesis of 3′-Deoxy-3′-18F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip

Hypervalent aryliodine compounds as precursors for radiofluorination

F-18 Labeled RGD Probes Based on Bioorthogonal Strain-Promoted Click Reaction for PET Imaging

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Efficient Radiosynthesis of 3′-Deoxy-3′-¹⁸F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip

Efficient Radiosynthesis of 3′-Deoxy-3′-¹⁸F-Fluorothymidine Using Electrowetting-on-Dielectric Digital Microfluidic Chip