• The Korean Journal of Nuclear Medicine Technology
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• v.22 no.1
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• pp.51-54
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• 2018

Purpose $^{18}F-THK5351$ is the newly developed PET probe for tau imaging in alzheimer's disease. The purpose of study was to establish the automated production of $^{18}F-THK5351$ on a commercial module. Materials and Methods Two different approaches were evaluated for the synthesis of $^{18}F-THK5351$. The first approach (method I) included the nucleophilic $^{18}F$-fluorination of the tosylate precursor, subsequently followed by pre-HPLC purification of crude reaction mixture with SPE cartridge. In the second approach (method II), the crude reaction mixture was directly introduced to a semi-preparative HPLC without SPE purification. The radiosynthesis of $^{18}F-THK5351$ was performed on a commercial GE $TRACERlab^{TM}$ $FX-_{FN}$ module. Quality control of $^{18}F-THK5351$ was carried out to meet the criteria guidelined in USP for PET radiopharmaceuticals. Results The overall radiochemical yield of method I was $23.8{\pm}1.9%$ (n=4) as the decay-corrected yield (end of synthesis, EOS) and the total synthesis time was $75{\pm}3min$. The radiochemical yield of method II was $31.9{\pm}6.7%$ (decay-corrected, n=10) and the total preparation time was $70{\pm}2min$. The radiochemical purity was>98%. Conclusion This study shows that method II provides higher radiochemical yield and shorter production time compared to the pre-SPE purification described in method I. The $^{18}F-THK5351$ synthesis by method II will be ideal for routine clinical application, considering short physical half-life of fluorine-18 ($t_{1/2}=110min$).

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.123-131
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• 2016

Increasing clinical demand for carbon-11 labeled radiopharmaceuticals has triggered technological advances in fields of radiochemistry and automated modules. Even though carbon-11 has a short half-life ($t_{1/2}=20.4min$), the consecutive second production of carbon-11 labeled radiopharmaceutical in one $^{11}C$-synthetic module should be delayed at least over 4 h to avoid the high radiation exposure. We herein aimed to produce two different carbon-11 labeled radiopharmaceuticals ([$^{11}C$]PIB and [$^{11}C$]methionine) by sharing of [$^{11}C$]methylation source in one $^{11}C$-synthetic module. The synthesis of $^{11}C$-labeling reagents ($[^{11}C]CH_3I$ or $[^{11}C]CH_3OTf$) is fully automated using the commercial TRACERlab $FX_{C-pro}$ module and is readily adaptable to $^{11}C$-labeling reactor for [$^{11}C$]PIB as well as another $^{11}C$-labeling apparatus for [$^{11}C$]methionine via the three-way valve. After completing the [$^{11}C$]PIB production, the re-synthesized $[^{11}C]CH_3I$ was passed through the three-way valve connected the polyetheretherketone (PEEK) line and loaded into the C18 Sep-Pak cartridge including the methionine precursor. The labeled product [^${11}C$]methionine was purified by a simple cartridge separation and reformulated into saline. The radiochemical yield of [$^{11}C$]PIB and [$^{11}C$]methionine were $5.3{\pm}0.6%$ and $18.7{\pm}0.8%$ (n.d.c.), respectively, with over 97% of radiochemical purity. The specific activity of [$^{11}C$]PIB was over $110GBq/{\mu}mol$. Total production time of two radiopharmaceuticals needs about 2 h from $1^{st}$ beam irradiation including quality control tests. Final [$^{11}C$]PIB and [$^{11}C$]methionine were satisfied all quality control test standards.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.440-451
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• 1997

This study was designed to prospect the $^{111}In$-labelled paclitaxel as tumor imaging agent. In order to provide a taxol molecule with a functional group which is able to chelate In-111, taxol-DTPA conjugate and 2'-hemisuccinyltaxol were synthesized by esterification of taxol at C-2'on C-13 carbon with DTPA anhydride and succinic anhydride, respectively. Synthesis yield of the taxol derivatives was 34% for taxol-DTPA and 80% for 2'-hemisuccinyltaxol. Cytotoxicity of the taxol derivatives were measured by MTT method toward cell lines HT29, B16, P388, and CT26. The cytotoxic activities of the taxol derivatives were maintained, although less active than taxol. Radiolabelling of the taxol derivatives were proceeded directly with $^{111}InCl_3$ or indirectly with $^{111}In$-citrate(ligand-exchange method). The ligand-exchange method was not suitable because some precipitates appeared during the reaction. On the contrary, by direct radiolabelling method, we were able to obtain taxol-DTPA-$^{111}In$ in 100% radiochemical yield. However, 2'-hemisuccinyltaxol was not labelled by both methods. Yield and radiochemical purity of the radiolabelled com-pound were determined by HPLC, paper chromatography and instant thin layer chromatography. Taxol-DTPA-$^{111}In$ was characterized to be hydrophilic by lipophilicity test, and nearly non-adhesive to HT29, B16, P388, and CT26 by cell binding affinity test. Binding affinity of the taxol-DTPA-$^{111}In$ complex to serum proteins was also examined by protein precipitation with 30% trichloroacetic acid. The results showed that 30% of the taxol-DTPA-$^{111}In$ complex binds with serum proteins.

• The Korean Journal of Nuclear Medicine
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• v.36 no.2
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• pp.102-109
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• 2002

Purpose : In gene therapy, tumor cells expressing the herpes simplex virus thymidine kinase are sensitive to prodrugs. Potential prodrugs IVDU and IVFRU were synthesized and radiolabeled with radioiodine for noninvasive imaging of herpes simplex virus type 1 gene expression. Material and Methods : 5-(2-trimethysilyl) vinyl-2'-deoxyuridine and 5-(2-trimethylsilyl)vinyl-2'-fluoro-2'-deoxyuridine, precursors of 5-(2--iodo)viny l-2'-deoxy uridine(IVDU) and 5-(2-iodo)-2'-vinyl-2'-deoxy-2'-fluororibofuranosyl uracil(IVFRU), were synthesized from reaction of trans-1-trimethylsillyl-2-tri-n-butylstannylethylene with 5-iodo-2'-deoxyuridine and 5-iodo-2'-fluoro-2'-deoxyuridine, respectively, on the condition of Pd catalyst. These precursors were separated from reaction mixture by silica gel column chromatography method. Each precursor was radioiodinated with radioiodine by mixing with ICI oxidizing agent. These radioiodinated compounds were purified with HPLC. Radiohalogen exchange has been shown to be effective for the synthesis of products with lower specific activity. Similarly, carrier-added and high specific activity products have been isolated in respectable radiochemical yields using ICI method. Results : Synthetic yield of precursors, IVDU and IVFRU were 43% and 18%, respectively. Radiochemical purity of both compunds was over 98%. Conclusion : We synthesized precursors of IVDU and IVFRU for monitoring of HSV1-tk gene expression. Radiotracers were radioiodinated with high radiolabeling yield by ICI method.

• Bulletin of the Korean Chemical Society
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• v.26 no.1
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• pp.91-96
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• 2005

O-(3-[$^{18}$F]Fluoropropyl)-L-tyrosine (L-[$^{18}$F]FPT) was synthesized by nucleophilic radiofluorination followed by acidic hydrolysis of protective groups and evaluated with 9 L tumor bearing rat. L-[$^{18}$F]FPT is an homologue of O-(2-[$^{18}$F]fluoroethyl)-L-tyrosine (L-[$^{18}$F]FET) which recently is studied as a tracer for tumor imaging using positron emission tomography (PET). [$^{18}$F]FPT was directly prepared from the precursor of O-(3-ptoluenesulfonyloxypropyl)- N-(tert-butoxycarbonyl)-L-tyrosine methyl ester. FPT-PET image was obtained at 60 min in 9 L tumor bearing rats. The radiochemical yield of [$^{18}$F]FPT was 0-45% (decay corrected) and the radiochemical purity was more than 95% after HPLC purification. The total time elapsed for the synthesis of [$^{18}$F]FPT was 100 min from EOB (End-of-bombardment). A comparison of uptake studies between [$^{18}$F]FPT and [$^{18}$F]FET was performed. In biodistribution, [$^{18}$F]FPT showed similar pattern with [$^{18}$F]FET in various tissues, but [$^{18}$F]FPT showed low uptake in brain. Furthermore, [$^{18}$F]FPT showed higher tumor-to-brain ratio than [$^{18}$F]FET. In conclusion, [$^{18}$F]FPT seems to be more useful amino acid tracer than [$^{18}$F]FET for brain tumors imaging with PET.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.6
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• pp.561-565
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• 2007

Purpose: Lipophilic cations including tetraphenylphosphonium (TPP) salts penetrate the hydrophobic barriers of the plasma and mitochondrial membranes, resulting in accumulation in mitochondria in response to the negative inner transmembrane potentials. The development of radiolabeled phosphonium cations as a noninvasive imaging agent may serve as a new molecular "voltage sensor" probe to investigate the role of mitochondria in the pathophysiology and diagnosis of cancer. Materials and Methods: We have synthesized a reference compound (4-fluorophenyl)triphenylphosphonium (TPP) and a labeled compound $[^{18}F]$TPP via two step nucleophilic substitution of no-carrier-added $[^{18}F]$fluoride with the precursor, 4-iodophenyltrimethylammonium iodide, in the presence of Kryptofix-2.2.2 and $K_2CO_3$. Result: The reference compound (4-fluorophenyl)triphenylphosphonium (TPP) was synthesized in 60% yield. The radiolabeled compound $[^{18}F]$TPP was synthesized in $10\sim15%$ yield. The radiochemical purity of the $[^{18}F]$TPP was $95.57{\pm}0.51%$ (n=11). Conclusion: $[^{18}F]$TPP was successfully synthesized that might have a potential to be utilized as a novel myocardial or cancer imaging agent for PET. However, it is required to improve the radiochemical yield to apply $[^{18}F]$TPP in preclinical or clinical researches.

• Journal of the Korean Chemical Society
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• v.17 no.1
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• pp.15-19
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• 1973

A method was developed for the separation of titanium, niobium and zirconium together in a group from the coexisting ions of various metals such as iron, cobalt, nickel, yttrium and rare earths by means of the cation exchange column using ${\alpha}$-hydroxyisobutyric acid as the eluent. In the course of the present investigation, it was found that the tailing phenomena of zirconium were attributable to the hydroxide precipitation which was made prior to the elution. For example, if zirconium was precipitated by sodium hydroxide, the tailing of zirconium became very serious in contrast to the results reported by others. This paper describes how these tailing phenomena of zirconium were prevented and how a practical procedure for the separation of these ions was, achieved using ion-exchange method. Using the present method the nuclides of $^{90m}Y$ and $^{90}Y$ were separated with radiochemical purity from the irradiated zirconium.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.2 no.2
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• pp.84-95
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• 2016

Considerably increasing interest in using the theranostic isotopes/ isotope pairs of radiometals like $^{44/47}Sc$ and $^{64/67}Cu$ for diagnosis and/or therapeutic applications in the nuclear medicine procedures necessitates its reliable production and supply. Separation and purification of no-carrier-added (NCA) isotopes from macro quantitates of the irradiated target matrix along with other impurities is a cardinal procedure amongst several other steps involved in its production. Multitudinous methods including but not limited to liquid-liquid (solvent) extraction, extraction chromatography (EXC), ion exchange, electrodeposition and sublimation are routinely applied either solitarily or in combination for the separation and purification of radioisotopes depending on their production routes, radioisotope of interest and impurities involved. However, application of EXC though has shown promises towards the numerous separation techniques have not received much attention as far as its application prospects in the field of nuclear medicine are concerned. Advances in the recent past for application of the EXC resins in separation and purification of the several medically important radioisotopes at ultra-high purity have shown promising behavior with respect to their operation simplicity, acidic and radiolytic stability, separation efficiencies and speedy procedures with the enhanced and excellent extraction abilities. In this mini review we will be talking about the recent developments in the application and the use of EXC techniques for the separation and purification of $^{44/47}Sc$ and $^{64/67}Cu$ for medical applications. Furthermore, we will also discuss the scientific and practical aspects of EXC in the view of separation of the NCA trace amount of radionuclides.

• Biomedical Science Letters
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• v.3 no.2
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• pp.131-138
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• 1997

IgG-$^{188}$Re conjugate was prepared for the diagnosis of abscess. The IgG molecules reduced by 2-mercaptoethanol contained 1.5 free sulfhydryl groups per IgG molecule. The reduced IgG molecule was labelled with $^{188}$Re through chelate to 99％ of labelling yield. The radiochemical purity of IgG-$^{188}$Re conjugate was maintained at 90％ in the presence of human serum for 1 hour. The IgG-$^{188}$Re was intravenously administered into staphylococcal abscess-bearing rats and their biodistribution was monitored at 4 and 24 hours post injection. The IgG-$^{188}$Re conjugate was moderately localized in the abscess tissue. This result implies that the IgG-$^{188}$Re conjugate can be a tool for abscess diagnosis. This technique can be applied for the preparation of various monoclonal antibody labelled with $^{188}$Re.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.1 no.2
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• pp.137-144
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• 2015

Hypoxia is an important adverse prognostic factor for tumor progression and is a major cause of failure of radiation therapy. In case of short-term hypoxia, the metabolism can recover to normal, but if hypoxia persists, it causes irreversible cell damage and finally leads to death. So a hypoxia marker would be very useful in oncology. In particular, 2-nitroimidazole can be reduced to form a reactive chemical species, which can bind irreversibly to cell components in the absence of sufficient oxygen, thus, the development of radiolabeled nitroimidazole derivatives for the imaging of hypoxia remains an active field of research to improve cancer therapy result. 2-nitroimidazole based hypoxia marker, [$^{18}F$]FMISO holds promise for the evaluation of tumor hypoxia by Positron emission tomography (PET), at both global and local levels. In the present study, [$^{18}F$]FMISO was synthesized using an automatic synthesis module with high radiochemical purity (>99%) in 60 min. Immunohistochemical analysis using pimonidazole confirmed the presence of hypoxia in xenografted CT-26 tumor tissue. A biodistribution study in CT-26 xenografted mice showed that the increased tumor-to-muscle ratio and tumor-to-blood ratios from 10 to 120 min post-injection. In the PET study, [$^{18}F$]FMISO also showed increased tumor-to-muscle ratios from 10 to 120 min post-injection. In conclusion, this study demonstrates the feasibility and utility of [$^{18}F$]FMISO for imaging hypoxiain mouse colon cancer model using small animal PET.