ORCID Profile
0000-0001-5167-8063
Current Organisation
Universiti Putra Malaysia
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Publisher: MDPI AG
Date: 17-11-2022
DOI: 10.3390/MOLECULES27227969
Abstract: [18F]sodium fluoride ([18F]NaF) is recognised to be superior to [99mTc]-methyl diphosphate ([99mTc]Tc-MDP) and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in bone imaging. However, there is concern that [18F]NaF uptake is not cancer-specific, leading to a higher number of false-positive interpretations. Therefore, in this work, [18F]AlF-NOTA-pamidronic acid was prepared, optimised, and tested for its in vitro uptake. NOTA-pamidronic acid was prepared by an N-Hydroxysuccinimide (NHS) ester strategy and validated by liquid chromatography-mass spectrometry analysis (LC-MS/MS). Radiolabeling of [18F]AlF-NOTA-pamidronic acid was optimised, and it was ensured that all quality control analysis requirements for the radiopharmaceuticals were met prior to the in vitro cell uptake studies. NOTA-pamidronic acid was successfully prepared and radiolabeled with 18F. The radiolabel was prepared in a 1:1 molar ratio of aluminium chloride (AlCl3) to NOTA-pamidronic acid and heated at 100 °C for 15 min in the presence of 50% ethanol (v/v), which proved to be optimal. The preliminary in vitro results of the binding of the hydroxyapatite showed that [18F]AlF-NOTA-pamidronic acid was as sensitive as [18F]sodium fluoride ([18F]NaF). Normal human osteoblast cell lines (hFOB 1.19) and human osteosarcoma cell lines (Saos-2) were used for the in vitro cellular uptake studies. It was found that [18F]NaF was higher in both cell lines, but [18F]AlF-NOTA-pamidronic acid showed promising cellular uptake in Saos-2. The preliminary results suggest that further preclinical studies of [18F]AlF-NOTA-pamidronic acid are needed before it is transferred to clinical research.
Publisher: Springer Science and Business Media LLC
Date: 02-2021
DOI: 10.1007/S42452-021-04246-8
Abstract: Analytical gas chromatography in line with a flame ionization detector (GC-FID) method was developed and validated for direct determination of organic solvents in [ 18 F]fluoro-ethyl-tyrosine ([ 18 F]FET), [ 18 F]fluoromisonidazole ([ 18 F]FMISO) and [ 18 F]fluorothymidine ([ 18 F]FLT). Variables of the splitless time (min) and injection temperature ( ° C) on the response of analysis time and resolution were optimized with the assistance of a two-level full factorial design and desirability function of Derringer. The proposed procedure was validated following the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) guideline. Excellent linearity, R 2 0.990, indicated that approximately 99% of the response variance could be predicted from ethanol and acetonitrile concentrations ranging from 0.5 to 6.0 mg mL −1 and 0.1 to 0.8 mg mL −1 , respectively. The proposed procedure has proved to be selective, sensitive, and accurate (90–110%), with excellent repeatability and precision (RSD 2%). In the robustness analysis, the findings from the calculated Standardized Effects Values (SE) were insignificant ( p 0.05) and demonstrated that the proposed method was robust for a splitless time of 1.0 ± 0.5 min and an injection temperature of 210 ± 10 °C. The proposed method was also successfully used for the quantitative determination of ethanol and acetonitrile in [ 18 F]FET, [ 18 F]FMISO, and [ 18 F]FLT. Both solvents were well separated (R, 4.1–4.3) within 4.5 min. Therefore, the proposed method is relevant for routine quality control analysis of all 18 F-radiopharmaceutical derivatives for the direct determination of ethanol and acetonitrile.
Publisher: Bentham Science Publishers Ltd.
Date: 11-08-2016
DOI: 10.2174/1874471008666150804110923
Abstract: 18F-Fluorocholine has been suggested as one of the reputable imaging tracers for diagnosis of prostate tumour in Positron Emission Tomography / Computed Tomography (PET/CT) modality. Nevertheless, it has never been synthesised in Malaysia. We acknowledged that the major problem with 18F-Fluorocholine is due to its relatively low radiochemical yield at the end of synthesis (EOS). Therefore, this article presents improved 18FFluorocholine radiochemical yields after carrying out optimisation on azeotropic drying of 18F-Fluorine. In the previous study, the azeotropic drying of non-carrier-added (n.c.a) 18F-Fluorine in the reactor was conducted at atmospheric pressure (0 atm) and shorter duration time. In this study, however, the azeotropic drying of non-carried-added (n.c.a) 18FFluorine was made at a high vacuum pressure (- 0.65 to - 0.85 bar) with an additional time of 30 seconds. At the end of the synthesis, the mean radiochemical yield was statistically compared between the two azeotropic drying conditions so as to observe whether the improvement made was significant to the radiochemical yield. From the paired s le t-test analysis, the improvement done to the azeotropic drying of non-carrier-added (n.c.a) 18F-Fluorine was statistically significant (p < 0.05). With the improvement made, the 18F-Fluorcholine radiochemical yield was found to have increase by one fold. Improved 18F-Fluorocholine radiochemical yields were obtained after the improvement had been done to the azeotropic drying of non-carrier-added (n.c.a) 18F-Fluorine. It was also observed that improvement made to the azeotropic drying of non-carrier-added (n.c.a) 18F-Fluorine did not affect the 18F-Fluorocholine quality control analysis.
Publisher: AIP
Date: 2013
DOI: 10.1063/1.4803636
Publisher: Bentham Science Publishers Ltd.
Date: 11-08-2016
DOI: 10.2174/1874471008666150527091956
Abstract: Prostate cancer continues to be the most prevalent cancer in men in Malaysia. As time progresses, the prospect of PET imaging modality in diagnosis of prostate cancer is promising, with on-going improvement on novel tracers. Among all tracers, 18F-Fluorocholine is reported to be a reputable tracer and reliable diagnostic technique for prostate imaging. Nonetheless, only 18F-Fluorodeoxyglucose (18F-FDG) is available and used in most oncology cases in Malaysia. With a small scale GMP-based radiopharmaceuticals laboratory set-up, initial efforts have been taken to put Malaysia on 18F-Fluorocholine map. This article presents a convenient, efficient and reliable method for quality control analysis of 18F-Fluorocholine. Besides, the aim of this research work is to assist local GMP radiopharmaceuticals laboratories and local authority in Malaysia for quality control analysis of 18F-Fluorocholine guideline. 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. 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. 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.
Publisher: Wiley
Date: 10-09-2015
DOI: 10.1002/JLCR.3347
Abstract: (18)F-Fluoromethylcholine ((18)F-FCH) has been suggested as one of the reputable imaging tracers for diagnosis of prostate tumour in PET/CT examination. Nevertheless, it has never been synthesised in Malaysia. We acknowledged the major problem with (18)F-FCH is due to its relatively low radiochemical yield at the end of synthesis (EOS). Therefore, this technical note presents improved (18)F-FCH radiochemical yields after carrying out optimisation on azeotropic drying of non-carrier-added (18)F-Fluorine.
Publisher: SPIE
Date: 03-05-2013
DOI: 10.1117/12.2017113
Publisher: OMICS Publishing Group
Date: 2014
Publisher: Bentham Science Publishers Ltd.
Date: 04-06-2021
DOI: 10.2174/1874471013999201027215704
Abstract: Organic solvents play an indispensable role in most of the radiopharmaceutical production stages. It is almost impossible to remove them entirely in the final formulation of the product. In this presented work, an analytical method by gas chromatography coupled with flame ionization detection (GC-FID) has been developed to determine organic solvents in radiopharmaceutical s les. The effect of injection hold time, temperature variation in the injection port, and the column temperature on the analysis time and resolution (R ≥ 1.5) of ethanol and acetonitrile were studied extensively. The experimental conditions were optimized with the aid of further statistical analysis thence, the proposed method was validated following the International Council for Harmonisation (ICH) Q2 (R1) guideline. The proposed analytical method surpassed the acceptance criteria including the linearity 0.990 (correlation coefficient of R 2 ), precision 2%, LOD, and LOQ, accuracy 90% for all solvents. The separation between ethanol and acetonitrile was acceptable with a resolution R 1.5. Further statistical analysis of Oneway ANOVA revealed that the increment in injection holding time and variation of temperature at the injection port did not significantly affect the analysis time. Nevertheless, the variation in injection port temperature substantially influenced the resolution of ethanol and acetonitrile peaks (p 0.05). The proposed analytical method has been successfully implemented to determine the organic solvent in the [ 18 F]fluoro-ethyl-tyrosine ([ 18 F]FET), [ 18 F]fluoromisonidazole ([ 18 F]FMISO), and [ 18 F]fluorothymidine ([ 18 F]FLT).
Publisher: Elsevier BV
Date: 02-2014
Publisher: Bentham Science Publishers Ltd.
Date: 11-2021
DOI: 10.2174/1573405617666210216091202
Abstract: Bone metastases are a common source of malignancy in the skeleton and occur much more often than primary bone cancer. Several works were being performed to identify early markers for bone metastasis and novel drug targets to improve patients& #039 quality of life. As some concerns exist with the [18F]sodiumfluoridein positron emission tomography (PET) bone imaging, there has been an increase in the number of targeted radiopharmaceutical markers for bone metastases imaging in its competitor, 68Ga. Since 18F properties are superior to those of 68Ga, there is a distinct motivation for developing 18F radiopharmaceuticals for bone metastases imaging.
Start Date: 2014
End Date: 2016
Funder: Ministry of Higher Education, Malaysia
View Funded ActivityStart Date: 2012
End Date: 2014
Funder: Universiti Putra Malaysia
View Funded ActivityStart Date: 2019
End Date: 2019
Funder: International Atomic Energy Agency
View Funded ActivityStart Date: 2012
End Date: 2014
Funder: Universiti Putra Malaysia
View Funded ActivityStart Date: 2013
End Date: 2015
Funder: Universiti Putra Malaysia
View Funded ActivityStart Date: 2017
End Date: 2020
Funder: Universiti Putra Malaysia
View Funded Activity