ABSTRACT
Objective:To synthesize N- 18F-fluoroethyl-tofacitinib, and explore its feasibility in the diagnosis of rheumatoid arthritis (RA). Methods:The " two-step method" was used to modify tofacitinib with 18F-fluoroethyl, and the labeling rate and radiochemical purity of the probe were measured by high performance liquid chromatography (HPLC), and the stabilities of the probe in vivo and in vitro were investigated. BALB/c mice (normal group; n=3) and collagen-induced arthritis (CIA) model mice (CIA group; n=3) were injected with N- 18F-fluoroethyl-tofacitinib and CIA model mice injected with tofacitirrib and N- 18F-fluoroethyl-tofacitinib were as blocking group ( n=3). All mice underwent microPET imaging and the percentage injection dose per gram of tissue (%ID/g) and the uptake ratio of inflamed joints to muscle (T/M) were calculated. One-way analysis of variance and the least significant difference (LSD) t test were used to analyze the data. Results:The synthesis time of N- 18F-fluoroethyl-tofacitinib was about 120 min, with the yield approximately 1%, the specific activity >13.6 GBq/μmol, and the radiochemical purity >99%. After the probe incubated with PBS, plasma or in vivo for 2 h, the radiochemical purity was still more than 95%. MicroPET imaging showed that 30 min after injection, the uptake of N- 18F-fluoroethyl-tofacitinib in the inflamed joints of CIA group was higher than that of normal group and blocking group ((10.22±1.64), (2.71±0.26) and (2.81±0.33) %ID/g; F=58.26, t values: 7.83, 7.67, P values: 0.001, 0.002). The T/M of CIA group was also higher than that of normal group and blocking group (24.73±5.77, 2.75±1.36 and 2.89±0.54; F=40.64, t values: 6.42, 6.53, P values: 0.003, 0.003). Conclusions:N- 18F-fluoroethyl-tofacitinib is successfully prepared and it is stable in vitro with good imaging performance in vivo. It may be used in clinic for the diagnosis of RA.
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Objective To develop the automated preparation of 18F-Alfatide II using newly-designed 18F-minireactor and perform 18F-Alfatide D microPET/CT imaging in tumor.Methods The automated preparation of 18F-Alfatide H was developed by using 18F-microreactor and water phase Al18F-chelating method,and the radiochemical yield and quality analysis were measured.The nude mice bearing breast tumor ZR-75-1 and nasopharyngeal tumor CNE1 were established(n = 3 respectively).MicroPET/CT imaging was performed at 0.5,1.0 and 2.0 h after the injection of 18F-Alfatide II.The region of interest(ROI)was depicted and the tumor/muscle(T/M)ratio was calculated.Results 18F-Alfatide II was automatically prepared with the total synthesis time of 40 min,the radiochemical yield of(28±6)%(no decay corrected,n=11),and the radiochemical purity >97%.All quality analysis indexes accorded with the radiopharmaceutical requirements.18F-Alfatide II microPET/CT images of ZR-75-1 and CNE1 tumors were clear due to the high radioactivity uptake of tumor lesions(T/M ratio was greater than 4.0 at 1.0 h after injection).Conclusion Based on the 18F-minireactor,the,8F-Alfatide II can be prepared successfully with short synthesis time and high radiochemical yield,which can help the application studies in 18F-Alfatide II microPET/CT imaging.
ABSTRACT
Objective To develop an automated control system of batch-reactor microfluidic device for the synthesis of PET tracers and to use it for the preparation of 18F-fluorodeoxyglucose (FDG).Methods The 18F microreactor was composed of polydimethylsiloxane (PDMS) microfluidic chip and customized glass microvessel integrated with stainless capillary tube as heater or cooler.PDMS chip was fabricated by silkscreen printing technology.The hardware control of digital and analog quantity of synthesizer was completed by organic integration programmable logic controller (PLC),micro air valve,temperature sensor,com pressed air source,direct current stabilized voltage source and vacuum pumps.The interface was designed using Kingyiew software.Thin-layer chromatography (TLC) was applied to measure the 18F-labeling yield and the radiochemical purity of 18F-FDG.Kryptofix (K2.2.2) content,residual acetonitrile content,traits,a septic and bacterial endotoxins levels were also tested.Results The size of the microfluidic device was 10 cm× 10 cm×15 cm.The size of the automated control system was similar to the desktop chassis.The amount of precursor used in the single synthesis of 18F-FDG was 2.5 mg.The radiochemical purity of 18F-FDG was higher than 95％,the labeling yield was (92.4± 1.4) ％ and the 18 F-FDG yield was (35.6± 5.6) ％ (decay corrected).The 18F-FDG product was clear and colorless,and the pH value was 6.2±0.4.The K2.2.2 con tent was less than 50 μg/g.The residual acetonitrile content was (12.8±2.6) μg/g.Both aseptic and bacte rial endotoxins tests were negative.Conclusions A batch-mode microfluidic device is developed and successfully applied to prepare 18F-FDG.It has the advantages of high integration,small size,less consumption of labeling precursor and easy programming.