• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.8 no.2
• /
• pp.71-76
• /
• 2022

Indigenous diagnostic dose of ¹³¹I-labeled meta-iodobenzylguanidine ([¹³¹I]mIBG) was prepared via Cu⁺ catalyzed isotope exchange reaction generated in situ by sodium metabisulfite for imaging of neuroblastoma tumor. [¹³¹I]mIBG was produced in overall 85-90% radiochemical yield. The average amount of radioactivity of [¹³¹I]mIBG was 2164 MBq (1998-2331MBq) with an average specific activity > 1000 MBq/mg at the end of synthesis. The radiochemical purity was ≥ 99.9% after purification through Dowex-1 × 8 ion exchange resin (100-150 mesh) at the date of preparation. The stability of [¹³¹I]mIBG at concentration 480-555 MBq/mL was > 97% at 4 ℃ after 4 days. The room temperature (25 ℃) stability of [¹³¹I]mIBG was > 98% after 24 h. Biodistribution of [¹³¹I]mIBG in patient showed uptake in salivary glands, liver, spleen and excreted though urinary bladder. Neuroendocrine medicated uptake into tumor lesion and metastatic sites were noted which strongly correlate with the morphological abnormalities of patient.

• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.6 no.2
• /
• pp.61-68
• /
• 2020

Aggregated neurofibrillary tangles (NFTs) are a pathological hallmark in Alzheimer's disease (AD) and many radiopharmaceuticals targeting NFTs have been developed so far. Among these, [¹⁸F]flortaucipir (TAUVID^TM) is the first approved radiopharmaceutical in the Food and Drug Administration (FDA) to image tau pathology. In the present study, we describe the optimized radiosynthetic method for the routine production of [¹⁸F] flortaucipir using a commercialized automation module (i.e. GE TRACERlab^TM FX_FN pro). [¹⁸F]Flortaucipir was prepared by nucleophilic substitution from its N-tert-butoxycarbonyl protected nitro precursor, tertbutyl 7-(6-nitropyridin-3-yl)-5H-pyrido[4,3-b]indole-5-carboxylate, at 130℃ for 10 min in dimethyl sulfoxide. The mean radiochemical yield was 20 ± 4.3% (decay-corrected, n = 47) with the molar activity of 218 ± 32 GBq/µmol at the end of synthesis. The radiochemical purity was determined to be above 95%. The overall production time including quality control is approximately 100min. The final produced [¹⁸F]flortaucipir injection meets the USP criteria for quality control. Thus, this fully automated system is validated for clinical use.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.26 no.2
• /
• pp.15-19
• /
• 2022

Purpose [⁶⁸Ga]PSMA-11 is needed the high reproducibility, excellent radiochemical yield and purity. In term of radiation safety, the radiation exposure of operator for its production also should be considered. In this work, we performed a comparative study for the fully automated synthesis of [⁶⁸Ga]PSMA-11 between non-cassette type and cassette type. Materials and Methods Two different type of modules (TRACERlab FX N pro for non-cassette type and BIKBox for cassette type) were used for the automated production of [⁶⁸Ga]PSMA-11. According to the previously identified elution profile, Only 2.5 ml with high radioactivity was used for the reaction. After adjusting the pH of the reaction solution with HEPES buffer solution, the precursor was added and reacted with at 95 ℃ for 15 minutes. The reaction mixture was separated and purified using a C18 light cartridge. The product was eluted with 50% EtOH/saline solution and diluted with saline. It was completed by sterilizing filter. In the non-cassette type, the aforementioned process must be prepared directly. However, in the cassette method, synthesis was possible simply by installing a kit that was already completed. Results Both total [⁶⁸Ga]PSMA-11 production time were 25±3(non-cassette type) and 23±3 minutes(cassette type). The radiochemical yield of the non-cassette type(65.5±5.7%) was higher than that of the cassette type(61.6±4.8%) after sterilization filter. The non-cassette type took about 120 minutes of preparation time before synthesis due to washing of synthesizer and reagent preparation. However, since the cassette type does not require washing and reagent preparation, it took about 20 minutes to prepare before synthesis. Both type of synthesizer had a radiochemical high purity(>99%). Conclusion The non-cassette type production of [⁶⁸Ga]PSMA-11 showed higher radiochemical yield and lower cost than the cassette type. However, The cassette type has an advantage in terms of preparation time, convenience, and equipment maintenance.

• 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.

• Bulletin of the Korean Chemical Society
• /
• v.33 no.2
• /
• pp.489-491
• /
• 2012

An $^{125}I$-labeled resveratrol derivative 1 was synthesized. It was purified by reverse phase HPLC. Radiochemical purity of the product was more than 98%, and the yield was 35% (decay-corrected). Its biodistribution in tumorbearing mice was studied. The results showed that the highest radioactivity was located in intestine and stomach. The biodistribution profile suggests that compound 1 can be effectively used as a promising imaging probe for intestine and stomach.

• The Korean Journal of Nuclear Medicine
• /
• v.18 no.1
• /
• pp.55-62
• /
• 1984

For an effective solid-phase labelling of protein with $^{125}I$, studies on the immobilization of lactoperoxidase(LPO) on the inner wall of polystyrene tubes were carried out. Labelling of bovine serum albumin(BSA) and insulin was also practiced using the LPO immobilized tubes. The immobilized enzyme of about $2.5{\mu}g/tube$ was sufficient for small scale labelling since the results of radio-paper chromatography of the labelling mixture of insulin indicated that the yields were sufficiently high(80%) even in the reactions conducted at room temperature for 60 sec. The results of the Sephadex column chromatography indicated that the labelled products were not contaminated with $LPO-^{125}I$, and the radiochemical purity of the products was more than 90%. In considering the general trend that the $^{125}I$ labelled protein obtained by using LPO maintains its intactness better than those obtained by using chloramine-T, together with the tendency of yield enhancing with increase of reactants-concentration, the LPO immobilized tube method is estimated to be one of the simple methods of labelling. The product might be applicable without further purification.

• Journal of Radiation Industry
• /
• v.5 no.4
• /
• pp.313-316
• /
• 2011

[$^{18}F$]FDG (2-[$^{18}F$] Fluoro-2-deoxy-D-Glucose), which is required Automated Synthetic Module for production, is most often used Radiopharmaceuticals in nuclear medicine. In this study, an Automated Synthesis Module was developed to produce FDG in two consecutive time when F-18 feds continuously by modifying a domestic FDG Automated Synthetic Module on structural geometry and control system. The results were showed that the Average Synthesis Yields on the developed Automated Synthetic Module were $45{\pm}3%$ (n=20), $50{\pm}3%$ (n=20) respectively. The Quality Control results, such as Radio TLC, Radiochemical purity, Gamma-counter, pH, LAL Test, Micro bacteria test, showed in same level with domestic [$^{18}F$]FDG Auto-Synthetic modules. Therefore, if some features were improved by considering the components life time and appearance, commercial sales can be expected because of low price and easy maintenance compared with foreign products.

• Journal of Radiopharmaceuticals and Molecular Probes
• /
• v.5 no.1
• /
• pp.48-53
• /
• 2019

A bone metastasis is an important factor for prognosis and treatment of breast or prostate cancer patients. [$^{18}F$]Sodium fluoride ([$^{18}F$]NaF) is a PET radiopharmaceutical that can detect bone metastasis. Conventional [$^{18}F$]NaF production process included radioactive metal impurities because the product was prepared by adding saline after beam irradiation to $[^{18}O]H_2O$. In this study, we apply the method of removing radionuclidic impurities. To meet the criteria prescribed by GMP in quality control, we designed the custom-made [$^{18}F$]NaF automatic module. The mean radiochemical yield was $82.1{\pm}4.4%$ (n = 32) productions for 3 years) and the total preparation time was 4 min. The final produced [$^{18}F$]NaF solution meets the USP criteria for quality control. Thus, this fully automated system is validated for clinical use.

• Korean Journal of Clinical Laboratory Science
• /
• v.53 no.1
• /
• pp.1-10
• /
• 2021

Radiopharmaceuticals are drugs that contain radioisotopes and are used in the diagnosis, treatment, or investigation of diseases. Radiopharmaceuticals must be manufactured in compliance with good manufacturing practice regulations and subjected to quality control before they are administered to patients to ensure the safety of the drug. Radiopharmaceuticals for administration to humans need to be sterile and pyrogen-free. Hence, sterility tests and membrane filter integrity tests are carried out to confirm the asepticity of the finished drug product, and a bacterial endotoxin test conducted to assess contamination, if any, by pyrogens. The physical appearance and the absence of foreign insoluble substances should be confirmed by a visual inspection. The chemical purity, residual solvents, and pH should be evaluated because residual by-products and impurities in the finished product can be harmful to patients. The half-life, radiochemical purity, radionuclidic purity, and strength need to be assessed by analyzing the radiation emitted from radiopharmaceuticals to verify that the radioisotope contents are properly labeled on pharmaceuticals. Radiopharmaceuticals always carry the risk of radiation exposure. Therefore, the time taken for quality control tests should be minimized and care should be taken to prevent radiation exposure during handling. This review discusses the quality control procedures and acceptance criteria for a diagnostic radiopharmaceutical.

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