• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.153-159
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• 2021

This article provides an efficient ¹⁸F-labeling protocol based on a rapid condensation reaction between 2-cyanobenzothiazole (CBT) and N-terminal cysteine-containing biomolecules. The ¹⁸F-labeled CBT (¹⁸F-1) was prepared by radiofluorination of the tosylated precursor 4 with 18-crown-6/K+/[¹⁸F]F- complex. Using the purified ¹⁸F-1, ¹⁸F-labeled peptide (¹⁸F-7) and protein (¹⁸F-8) could be synthesized efficiently under mild conditions. This strategy would provide a convenient approach for rapid and site-specific ¹⁸F-labeling of various peptides and proteins for in vivo imaging and biomedical applications.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.5 no.2
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• pp.145-151
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• 2019

Fluorine-18 is considered to be the radionuclide of choice for positron emission tomography (PET). Thus, the development of small molecule-based radiopharmaceuticals for use in diagnostic imaging relies heavily on efficient radiofluorination techniques. Until the early 2000s, diaryliodonium salts and aryliodonium ylides were widely employed as labeling precursors to yield aromatic PET radiotracers with cyclotron-produced [¹⁸F]fluoride ion. Rapid recent progress in the development of efficient borylation methods has led to a paradigm shift in ¹⁸F-labeling methods. In addition, deoxyfluorination has attracted a great deal of interest as an alternative approach to aryl ring activation with ¹⁸F^-. In this review, methods for radiolabel development are discussed with a specific focus on the progress made in the last 5 years. Other interesting ¹⁸F-based protocols are also briefly introduced. New methods for exploiting ¹⁸F^- are expected to increase the number of ¹⁸F-labeling methods, to allow applications in a range of chemical environments.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.10 no.1
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• pp.27-32
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• 2024

Prostate cancer (PCa) is the second most frequent cancer. Prostate specific membrane antigen (PSMA) is an effective target for the detection, staging and monitor the response of therapy in the management of PCa. In this study, we aimed to develop a ¹⁸F-labeled PSMA-PET tracer ([¹⁸F]AlF-ND-GUL) and test its feasibility for targeting PCa. A variety of labeling conditions was tested for optimization to achieve maximum radiolabeling efficiency. To test the imaging capacity of [¹⁸F]AlF-ND-GUL, in vivo PET/MR images were performed in 22Rv1 tumor bearing BALB/c nude mice after injection of radiotracer. Optimized labeling condition was to dissolve 300 nmol of precursor (ND-GUL) in buffer (pH 4, 0.1 M, NaOAc-HOAc) and react with [¹⁸F]AlF at 110℃ for 30 min. The [¹⁸F]AlF-ND-GUL maintained stability of >85% over 4 h. In-vivo molecular PET/MR imaging study results clearly showed high tumor uptake of [¹⁸F]AlF-ND-GUL over time. In conclusion, we optimized [¹⁸F]AlF-ND-GUL labeling conditions for PCa diagnosis and confirmed PSMA specific binding in vivo.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.3 no.1
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• pp.3-14
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• 2017

Nucleophilic aromatic fluorination has been one of the most explored methods in fluorin-18 based radiochemistry. Unlike electrophilic $[^{18}F]$fluorination methods, no-carrier-added nucleophilic radiofluorination with cyclotron-produced $[^{18}F]$fluoride ion offers better specific radioactivity which is essential aspect to obtain good quality images from positron emission tomography. Contrary to amenable aliphatic radiofluorination, the development of reliable aromatic $[^{18}F]$fluorination methods has been pursued by many research groups; however, no viable method has yet been established. Recently, hypervalent iodine compound draws increasing attention as versatile radiolabeling precursor for various $[^{18}F]$fluoroarenes, since it bears the capacity to introduce fluorine-18 either on electron-deficient or electron-rich aryl ring with enhanced regiospecificity. Other classes of hypervalent iodine congeners often utilized in radiochemistry are iodylarenes, iodonium ylides, and spirocyclic iodonium ylides. Recently developed spirocyclic iodonium ylides have already been avidly employed to provide various $[^{18}F]$aryl fluorides with high labeling efficiency. This metal-free protocol would afford efficient routes, replacing the traditional approaches to $[^{18}F]$fluoroarenes, from prosthetic labeling synthons to complex PET radiotracers.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.2
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• pp.91-99
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• 2009

Noninvasive imaging of molecular and biological processes in living subjects with positron emission tomography(PET) provides exciting opportunities to monitor metabolism and detect diseases in humans. Measuring these processes with PET requires the preparation of specific molecular imaging probes labeled with $^{18}F$-fluorine. In this review we describe recent methods and novel trends for the introduction of $^{18}F$-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic $^{18}F$-fluorination of some halo- and mesyloxyalkanes to the corresponding $^{18}F$-fluoroalkanes with $^{18}F$-fluoride obtained from an $^{18}O(p,n)^{18}F$ reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for $^{18}F$-fluorine labeling. Ionic liquid method is rapid and particularly convenient because $^{18}F$-fluoride in $H_2O$ can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. The nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with $^{18}F$-fluorine for PETimaging, and it is illustrated by the synthesis of $^{18}F$-fluoride radiolabeled molecular imaging probes, such as $^{18}F$-FDG, $^{18}F$-FLT, $^{18}F$-FP-CIT, and $^{18}F$-FMISO, in high yield and purity and in shorter times compared to conventional syntheses.

• Bulletin of the Korean Chemical Society
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• v.32 no.1
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• pp.71-76
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• 2011

An efficient nucleophilic [$^{18}F$]fluorination has been studied to reduce byproducts and preparation time. Instead of conventional aqueous solution of $K_2CO_3-K_{222}$, several organic solution containing inert organic salts were used to release [$^{18}F$]fluoride ion and anion bases captured in the polymer cartridge, concluding that methanol solution is the best choice. Comparing to azeotropic drying process, one min was sufficient to remove methanol completely, resulting in about 10% radioactivity saving by reducing drying time. The polymer cartridge, Chromafix$^{(R)}$ (PS-$HCO_3$) was pretreated with several anion bases to displace pre-loaded bicarbonate base. Phosphate bases showed better results than carbonate bases in terms of lower basicity. tert-Butanol solvent used as a reaction media played another critical role in nucleophilic [18F]fluorination by suppressing eliminated side product. Consequent [$^{18}F$]fluorination under the present condition afforded fast preparation of reaction solution and high radiochemical yields (98% radio-TLC, 84% RCY) with 94% of precursor remained.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.1
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• pp.15-22
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• 2015

$^{18}F$-labeling reaction of bioactive molecule via click chemistry is widely used to produce $^{18}F$-labeled radiotracer in the field of radiopharmaceutical science and molecular imaging. In particular, bioorthogonal strain-promoted alkyne-azide cycloaddition (SPAAC) reaction has received much attention as an alternative ligation method for radiolabeling bioactive molecules such as peptides, DNA, proteins as well as nanoparticles. Moreover, SPAAC based pretargeting method could provide tumor images successfully on positron emission tomography system using nanoparticle such as mesoporous silica nanoparticles.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.104-109
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• 2010

Purpose: $[^{18}F]$Fallypride plays an effective radiotracer for the study of dopamine $D_2/D_3$ receptor occupancy, neuropsychiatric disorders and aging in humans. This tracer has the potential for clinical use, but automated labeling efficiency showed low radiochemical yields about 5~20% with relatively long labelling time of fluorine-18. In present study, we describe an improved automatic synthesis of [$^{18}F$]Fallypride using different base concentration for routine clinical use. Materials and Methods: Fully automated synthetic process of [$^{18}F$]Fallypride was perform using the TracerLab $FX_{FN}$ synthesizer under various labeling conditions and tosyl-fallypride was used as a precursor. [$^{18}F$]Fluoride was extracted with various concentration of $K_{2.2.2.}/K_2CO_3$ from $^{18}O$-enriched water trapped on the ion exchange cartridge. After azeotropic drying, the labeling reaction proceeded in $CH_3CN$ at $100^{\circ}C$ for 10 or 30 min. The reaction mixture was purified by reverse phase HPLC and collected organic solution was exchanged by tc-18 Sep-Pak for the clinically available solution. Results: The optimal labeling condition of [$^{18}F$]Fallypride in the automatic production was that 2 mg of tosyl-fallypride in acetonitrile (1 mL) was incubated at $100^{\circ}C$ for 10 min with $K_{2.2.2.}/K_2CO_3$ (11/0.8 mg). [$^{18}F$]Fallypride was obtained with high radiochemical yield about $66{\pm}1.4%$ (decay-corrected, n=28) within $51{\pm}1.2$ min including HPLC purification and solid-phase purification for the final formulation. Conclusion: [$^{18}F$]Fallypride was prepared with a significantly improved radiochemical yield with high specific activity and shorten synthetic time. In addition, this automated procedure provides the high reproducibility with no synthesis failures (n=28).

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.10 no.1
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• pp.51-62
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• 2024

Boron neutron capture therapy (BNCT) stands at the forefront of cancer treatment, offering a pioneering approach to enhance the rate of recovery for patients who show noncompliance to conventional therapies. The ¹⁸F labeling of BNCT tracers signifies a groundbreaking leap in molecular imaging. Hence, the aim of this brief review is to outline the radiofluorination strategies utilized for BNCT tracers. Radiofluorination of L-BPA, a ligand of L-type amino acids, can be carried out via electrophilic as well as nucleophilic substitution reactions. It's solubility can be elevated by complexing it with fructose to form BPA-fructose complex, followed by radiolabeling with ¹⁸F. In addition to electrophilic and nucleophilic radiofluorination, we have briefly presented the radiofluoro exchange method, which is applicable for amino acids having trifluoroborate groups, i.e., FBY (fluoroboronotyrosine), featuring both imaging and therapeutic functionalities. Furthermore, this review offers an inclusive array of radiofluorination strategies employed for other BNCT tracers, including o-carborane and fenbufen boronopinacol.

• Bulletin of the Korean Chemical Society
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• v.25 no.4
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• pp.506-510
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• 2004

There have been intensive studies concerning $[^{11}F]$choline ($[^{11}F]$methyldimethyl( ${\beta}$ -hydroxyethyl) ammonium) (1) which is known as a very effective tracer in imaging various human tumors localized in brain, lung, esophagus, rectum, prostate and urinary bladder using Positron Emission Tomography (PET) and there is increasing interest in $^{18}F$ labelled choline (2) and proved to be useful to visualize prostate cancer. We have prepared six $^{18}F$ labelled alkyl choline derivatives (3a-3c, 4a-4c) from ditosylated and dibrominated alkanes in moderate yields. The six alkyl tosylate or bromate ammonium salts have been synthesized as precursors. Radiofluorination was achieved by the treatment of precursors with $^{18}F$ - in the presence of Kryptofix-2.2.2.. The labeling yields varied ranging from 7 to 25%.