METHODS: In this study, prior to synthesis, quality control analysis method for 18F-Fluorocholine was developed and validated, by adapting the equipment set-up used in 18F-Fluorodeoxyglucose (18FFDG) routine production. Quality control on the 18F-Fluorocholine was performed by means of pH, radionuclidic identity, radio-high performance liquid chromatography equipped with ultraviolet, radio- thin layer chromatography, gas chromatography and filter integrity test.
RESULTS: Post-synthesis; the pH of 18F-Fluorocholine was 6.42 ± 0.04, with half-life of 109.5 minutes (n = 12). The radiochemical purity was consistently higher than 99%, both in radio-high performance liquid chromatography equipped with ultraviolet (r-HPLC; SCX column, 0.25 M NaH2PO4: acetonitrile) and radio-thin layer chromatography method (r-TLC). The calculated relative retention time (RRT) in r-HPLC was 1.02, whereas the retention factor (Rf) in r-TLC was 0.64. Potential impurities from 18F-Fluorocholine synthesis such as ethanol, acetonitrile, dimethylethanolamine and dibromomethane were determined in gas chromatography. Using our parameters, (capillary column: DB-200, 30 m x 0.53 mm x 1 um) and oven temperature of 35°C (isothermal), all compounds were well resolved and eluted within 3 minutes. Level of ethanol and acetonitrile in 18F-Fluorocholine were detected below threshold limit; less than 5 mg/ml and 0.41 mg/ml respectively. Meanwhile, dimethylethanolamine and dibromomethane were undetectable.
CONCLUSION: A convenient, efficient and reliable quality control analysis work-up procedure for 18FFluorocholine has been established and validated to comply all the release criteria. The convenient method of quality control analysis may provide a guideline to local GMP radiopharmaceutical laboratories to start producing 18F-Fluorocholine as a tracer for prostate cancer imaging.
METHODS: Valproic acid-encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in-vitro blood-brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain.
KEY FINDINGS: Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In-vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE-treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half-life and reduction in clearance compared to VPA. Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half-life of VPA by encapsulating it within the nanoemulsion-T80.
CONCLUSIONS: Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA.