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

• Nuclear Medicine and Molecular Imaging
• /
• v.43 no.1
• /
• pp.1-9
• /
• 2009

As many new drug substances contained various aromatic rings and fluorine attached to an electron rich aromatic ring or on the meta-position, a strategy towards improvement in aromatic fluorination of these compounds is highly desirable. The introduction of fluorine-18 onto aromatic rings showed in the limited condition containing electron withdrawing group (EWG) on the para- or ortho-position to get reasonable radiochemical yield so far. No-carrier added (NCA) [$^{18}F$]fluoroarene syntheses by iodonium salts recently reported that has the potential to greatly increase the yield in systems or positions that normally not reactive enough to give sufficient yields in simple model reaction. This review describes the methodological approach towards effective aromatic fluorination by diaryliodonium salts and future prospects in an application of novel PET radiotracer.

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

• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.5 no.1
• /
• pp.18-25
• /
• 2019

2-Nitroimidazole derivatives have been reported to accumulate in hypoxic tissue. We prepared a novel $^{99m}Tc-MAG_3$-2-nitroimidazole and evaluated the feasibility for hypoxia imaging agent. $Bz-MAG_3$-2-nitroimidazole was synthesized by direct coupling of $Bz-MAG_3$ and 2-nitroimidazole using dicyclohexylcarbodiimide. $Bz-MAG_3$-2-nitroimidazole was labeled with $^{99m}Tc$ in the presence of tartaric acid and $SnCl_2-2H_2O$ at $100^{\circ}C$ for 30 min. And the reaction mixture was purified by $C_{18}$ Sep-pak cartridge. The labeling efficiency and the radiochemical purity were checked by ITLC-SG/acetonitrile. The tumor was grown in balb/c mice for 8~13 days after the subcutaneous injection of tumor cells, CT-26 (murine colon adenocarcinoma cell). Biodistribution study and tumor autoradiography were performed in the xenografted mice after i.v injection of 74 kBq/0.1 mL and 19 MBq/0.1 mL of $^{99m}Tc-MAG_3$-2-nitroimidazole, respectively. In vivo images of $^{99m}Tc-MAG_3$-2-nitroimidazole in tumor bearing mice were obtained 1.5 hr post injection. The labeling efficiency was $45{\pm}20%$ and the radiochemical purity after purification was over 95%. Paper electrophoresis confirmed negative charge of $^{99m}Tc-MAG_3$-2-nitroimidazole. $^{99m}Tc-MAG_3$-2-nitroimidazole was very stable at room temperature and its protein binding was 53%. The $^{99m}Tc-MAG_3$-2-nitroimidazole exhibited high uptake in the liver, stomach and intestine. In biodistribution study using tumor bearing mice, the uptakes (% ID/g) of the tumor were $0.5{\pm}0.1$, $0.4{\pm}0.0$, $0.2{\pm}0.1$ and $0.1{\pm}0.1$ at 5, 15, 30 min and 4 hrs. Tumor/muscle ratio were $1.4{\pm}0.1$, $2.2{\pm}0.83$, $3.0{\pm}0.9$, and 3.7 (n=2) for 5, 15, 30 min and 4 hrs. The uptake in hypoxic area was found higher than in non-hypoxic area of tumor tissue by autoradiography. In vivo images showed the relatively faint uptake to the hypoxic tumor region. $^{99m}Tc-MAG_3$-2-nitroimidazole was successfully synthesized and found feasible for imaging hypoxia.

• The Korean Journal of Nuclear Medicine
• /
• v.28 no.3
• /
• pp.331-337
• /
• 1994

In order to develop a $^{18}F$-labelled myocardial perfusion agent(flow tracer) for PET, $^{18}F$-labelled organic ammonium cations were synthesized and evaluated in relation to their biodistribution. Five quaternary organic ammonium compounds were labelled with $^{18}F$ in a side chain with moderate to good yields by direct introduction of $^{18}F$-fluoride. Radiochemical yields have been achieved in 30-40min by the precursors (tosylates) in dimethylsulfoxide 15-60% (decay corrected). The reaction was found to be autocatalyzed. A remote controlled procedure was developed in these synthesis. $^{18}F$-Labelling and HPLC-purification of com-pounds needed about 60 min(Yield; 7-20%). Up to now the two compounds N-4-[$^{18}F$]fluorobutyl-pyridinium cation(1) and N, N dibenzyl-4(2-[$^{18}F$]fluoroethyl)piperidinium cation(2) were investigated in relation to their biodistribution in mice. Compound 1 showed at 1 min post injection the high uptake of 19.22% ID/g organ in the myocardium but a following fast decline to 1.12% ID/g organ after 40min. Uptake of compound 2 was after 1min in the heart 5.90% ID/g organ but after 40min at the relative high value of 4.33% ID/g organ. Heart:blood ratio for compound(1) at 1 min was 8.3, at 40 min 2.6 for compound II 2.0(1min) and 15.0(40 min). As data of compound 2 showed greater heart uptake, slower myocardial release, and higher heart: blood ratios, compound 2 is a good candidate for further evaluation.

• The Korea Journal of Herbology
• /
• v.23 no.1
• /
• pp.117-125
• /
• 2008

Objectives : This study was to verify the Attributive Channel theory of herbal medicine. Methods : [$^{131}I$]iodohesperetin was synthesized, separated, and refined from hesperetin, the major component of Citrus species, followed by observing the biodistribution in an organism of C57 BL/6 mice with and without Lewis Lung Carcinoma. Results : Iodohesperetin 27.5 mg was obtained through column cliromatography after a reaction with 50 mg of Hesperitin and 8 mg of Nal. The radiochemical yield of [$^{131}I$]iodohesperetin synthesis was 25 % when checked with Radio TLC chromatography. [131I]iodohesperetin was most largely distributed in the stomach, lung and liver of C57BL/6 mouse. The highest %ID/g in stomach was 40 min, in lung and liver was 20 min after injection. The % ID/g of tumor tissue was comparable with that of blood. Conclusions : The fact that [$^{131}I$]iodocurcumin was most largely distributed in the stomach, lung and liver was related with the Attributive Channel theory. And there was no significant finding related to tumor cells.

• The Korean Journal of Nuclear Medicine
• /
• v.29 no.1
• /
• pp.105-109
• /
• 1995

L-3-[$^{123}I$]iodo-${\alpha}$-methyltyrosine([$^{123}I$] IMT) was synthesized by electrophilic radio-iodination using chloramine-T and Iodobead in phosphate buffered solution. And the biodistribution was examined in 9L glioma bearing rats. The radiosynthesis of [$^{123}I$]IMT with iodobead was simpler and higher in radiochemical yield(88%) than the method using chloramine-T(83%) as radioiodinating reagent. The highest yield was obtained from the reaction using 1 piece of Iodobead, $200{\mu}g$ ${\alpha}$-methyltyrosine in $100{\mu}l$ phosphate-buffered solution(pH 5.5) and the reaction was completed in 7min. 24 hours after the injection, the biodistribution in 9L glioma transplanted rats revealed the in vivo deiodination, the excretion via kidney, and 3 times higher uptake in the tumor than normal brain. These results suggest the promising clinical use of [$^{123}I$] IMT in the various malignancies.

• The Korean Journal of Nuclear Medicine
• /
• v.39 no.1
• /
• pp.44-48
• /
• 2005

Purpose: Ethylenediamine-tetramethylenephosphonic acid (EDTMP) has widely used chelator for the labeling of bone seeking radiopharmaceuticals complexed with radiometals. $^{153}Sm$ can be produced by the HANARO reactor at the Korea Atomic Energy Research Institute, Taejon, Korea. $^{153}Sm$ has favourable radiation characteristics $T1/2=46.7\;h,\;{\beta}_{max}=0.81\;MeV\;(20%),\;0.71\;MeV\;(49%),\;0.64\;MeV\;(30%)\;and\;{\gamma}=103\;keV\;(30%)$ emission which is suitable for imaging purposes during therapy. We investigated the labeling condition of $^{153}Sm$-EDTMP and imaging of $^{153}Sm$-EDTMP in normal rats. Materials and methods: EDTMP 20 mg was solved in 0.1 mL 2 M NaOH. $^{153}SmCl^3$ was added to EDTMP solution and pH of the reaction mixtures was adjusted to 3 and 12, respectively. Radiochemical purity was determined with paper chromatography. After 30 min. reaction, reaction mixtures were neutralized to pH 7.4, and the stability was estimated upto 120 hrs. Imaging studies of each reaction were perfomed in normal rats (37 MBq/0.1 mL). Results: The labeling yield of $^{153}Sm$-EDTMP was 99%. The stability of pH 8 reaction at 60, 96 and 120 hr was 99%, 95%, 89% and that of pH 12 at 36, 60, 96 and 120 hr was 99%, 95%, 88%, 66%, respectively. The $^{153}Sm$-EDTMP showed constantly higher bone uptake from 2 to 48 hr after injection. Conclusion: $^{153}Sm$-EDTMP, labeled at pH 8 reaction condition, has been stably maintained. Image of $^{153}Sm$-EDTMP at 2, 24, 48 hr after injection, demonstrate that $^{153}Sm$-EDTMP is a good bone seeking radiopharmaceuticals.

• The Korean Journal of Nuclear Medicine
• /
• v.35 no.3
• /
• pp.185-191
• /
• 2001

Objectives: Recently, $[methyl-^{11}C]-({\beta}$-Hydroxyethyl)trimethylammonium ($[^{11}C]$choline) Has been discovered to be a very effective tracer in imaging various human tumors using positron omission tomography. Because of the short half-life of C-11, it is very difficult to use in a routine imaging procedure and needs a frequent synthesis of $[^{11}C]$choline. This can be supplemented by the substitution of $[^{11}C]$choline with $[methyl-^{18}F]$fluorocholine. Here, we would like to report ceil uptake and biodistribution of $[^{11}C]$choline and $[^{18}F]$fluorocholine as a basic study. Methods: $[^{11}C]$Choline was prepared by the treatment of $[^{11}C]CH_3I$ with N,N-dimethylaminoethanol and $[^{18}F]$fluorocholine was synthesized from reaction of $CH_2Br[^{18}F]F$ with N,N-dimethylaminoethanol. The radiochemical purity was checked by high performance liquid chromatography (HPLC). The blodistribution of $[^{11}C]$choline and $[^{18}F]$fluorocholine was determined in balb/c mouse at 5 min, 20 min, 40 min and 80 min. The cell uptake was measured using glioma (9L) and colon adenocarcinoma (SW620). Results: The radiochemical purity was more than 98% after purification. In the liver, uptake did not change over time; the uptake was 20%ID/g for $[^{11}C]$choline and 13%ID/g for $[^{18}F]$fluorocholine. In the kidney, radioactivity decreased over time; the uptake was 15%ID/g for $[^{11}C]$choline and 20%ID/g for $[^{18}F]$fluorocholine, 80 min post-injection. The cell uptake of $[^{11}C]$choline was 4.93% for glioma (9L) and 18.69% for colon adenocarcinoma (SW620). For $[^{18}F]$fluorocholine, 1.77% for glioma (9L) and 2.77% for colon adenocarcinoma (SW620). Conclusion: $[^{11}C]$Choline and $[^{18}F]$fluorocholine showed a different cell uptake tendency, depending on cancer cell line.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.13 no.3
• /
• pp.147-151
• /
• 2009

Purpose: 2-[$^{18}F$]Fluoro-2-deoxy-D-glucose ([$^{18}F$]FDG) particularly plays as a important role in Positron Emission Tomography (PET) imaging in nuclear medicine. Domestic [$^{18}F$]FDG auto synthesizers are installed in Seoul National University Bundang Hospital (SNUBH) at June 2008, these modules were known that it's synthetic yields were guaranteed in average $45{\pm}5%$ so far. To improve yields and convenience of domestic [$^{18}F$]FDG auto synthesizer, numerous trials in reaction time, base concentration, pressure and temperature were performed to increase [$^{18}F$]FDG yields. Materials and Methods: Several synthetic factors (temperature, time and pressure) and shortcoming were corrected based on many evaporation test. Syringe dispensing of tetra-butylammonium bicarbonate (TBAB) was replaced with micro pipette to prepare tetrabutyl ammonium fluoride salt ([$^{18}F$]TBAF). Troublesome refill of liquid nitrogen every 2 hours which was used to protect vacuum system was changed to charcoal cartridge, base guard filter. To monitor the volume of delivered $[^{18}O]OH_2$ from cyclotron by surveillance camera, we set up the volumetric vial on the cover of the module. In addition to, the recovery vial was added in [$^{18}F$]FDG production system to recover [$^{18}F$]FDG loss due to the leak of valve ($V_{13,14}$) in [$^{18}F$]FDG purification process. Results: When we used micro pipette for adding TBAB ($30\;{\mu}L$ in 12% $H_2O$ in acetonitrile), this quantitative dispensation has enabled to improve $5.5{\pm}1.7%$ residual fluorine-18 activity in fluorine separation cartridge compared to syringe adding. Besides, the synthetic yields of [$^{18}F$]FDG has increased $58{\pm}2.6%$ (n=19), $58{\pm}2.9%$ (n=14), $60%{\pm}2.5%$ (n=17) for 3 months. The life cycle of charcoal cartridge and base vacuum was 3 months prior to filling liquid nitrogen every 2 hours and additional side separator can prevent pump corrosion by organic solvent. After setting of volumetric indicator vial, the operator can easily monitor the total volume of irradiated $[^{18}O]OH_2$ from cyclotron. The recovery vial can be used for the stabilizer when an irregular [$^{18}F$]FDG loss was generated by the leak of valves ($V_{13,14}$). Conclusions: We has optimized appropriate synthetic conditions (temperature, time, pressure) in domestic [$^{18}F$]FDG auto synthesizer. In addition to, the remodeling with several accessories improve yields of domestic [$^{18}F$]FDG auto synthesizer with reliable reproducibility.