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  1. Sujá F, Yusof A, Osman MA
    Water Sci Technol, 2010;61(2):389-96.
    PMID: 20107265 DOI: 10.2166/wst.2010.825
    Leachate samples collected from the Ampar Tenang open dumping site at Dengkil, Malaysia, were analyzed for acute toxicity. Two in vivo toxicity tests, Acute Oral Toxicity (AOT) and Primary Skin Irritation (PSI), were performed using Sprague Dawley rats and New Zealand Albino rabbits, respectively. The leachate samples were also analyzed chemically for nitrate and phosphate, ammonia-nitrogen, Kjeldahl-nitrogen and Chemical Oxygen Demand (COD). Results from both the AOT and PSI tests showed that the leachate did not contribute to acute toxicity. The AOT test yielded a negative result: no effect was observed in at least half of the rat population. The PSI test on rabbits produced effects only at a leachate concentration of 100%. However, the skin irritation was minor, and the test returned a negative result. The four chemical tests showed high levels of nutrient pollution in the leachate. The nitrate and phosphate concentrations were 2.1 mg/L and 23.6 mg/L, respectively. Further, the ammonia-nitrogen concentration was 1,000 mg NH(3)-N/L the Kjeldahl-nitrogen level was 446 mg NH(3)-N/L, and the Chemical Oxygen Demand was 1,300 mg/L. The in vivo toxicity and chemical analyses showed that the leachate is polluted but not acutely toxic to organisms.
  2. Ch'ng YH, Osman MA, Jong HY
    Malays J Med Sci, 2021 Apr;28(2):161-170.
    PMID: 33958970 DOI: 10.21315/mjms2021.28.2.15
    Background: Specific language impairment (SLI) diagnosis is inconvenient due to manual procedures and hardware cost. Computer-aided SLI diagnosis has been proposed to counter these inconveniences. This study focuses on evaluating the feasibility of computer systems used to diagnose SLI.

    Methods: The accuracy of Webgazer.js for software-based gaze tracking is tested under different lighting conditions. Predefined time delays of a prototype diagnosis task automation script are contrasted against with manual delays based on human time estimation to understand how automation influences diagnosis accuracy. SLI diagnosis binary classifier was built and tested based on randomised parameters. The obtained results were cross-compared to Singlims_ES.exe for equality.

    Results: Webgazer.js achieved an average accuracy of 88.755% under global lighting conditions, 61.379% under low lighting conditions and 52.7% under face-focused lighting conditions. The diagnosis task automation script found to execute with actual time delays with a deviation percentage no more than 0.04%, while manually executing time delays based on human time estimation resulted in a deviation percentage of not more than 3.37%. One-tailed test probability value produced by both the newly built classifier and Singlims_ES were observed to be similar up to three decimal places.

    Conclusion: The results obtained should serve as a foundation for further evaluation of computer tools to help speech language pathologists diagnose SLI.

  3. Tan YN, Ayob MK, Osman MA, Matthews KR
    Lett Appl Microbiol, 2011 Nov;53(5):509-17.
    PMID: 21848644 DOI: 10.1111/j.1472-765X.2011.03137.x
    The goal of this study was to determine inhibitory effect of palm kernel expeller (PKE) peptides of different degree of hydrolysis (DH %) against spore-forming bacteria Bacillus cereus, Bacillus circulans, Bacillus coagulans, Bacillus licheniformis, Bacillus megaterium, Bacillus pumilus, Bacillus stearothermophillus, Bacillus subtilis, Bacillus thuringiensis, Clostridium perfringens; and non-spore-forming bacteria Escherichia coli, Lisinibacillus sphaericus, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella Typhimurium and Staphylococcus aureus.
  4. Thanapairoje K, Junsiritrakhoon S, Wichaiyo S, Osman MA, Supharattanasitthi W
    J Basic Clin Physiol Pharmacol, 2023 May 01;34(3):277-289.
    PMID: 36631934 DOI: 10.1515/jbcpp-2022-0242
    Ageing is the process generated by senescent cells, free radicals, inflammation and other relevant factors. Ageing contributes to age-related diseases that affect the quality of life. People are interested in anti-ageing intervention and many scientists attempt to search for anti-ageing medicines. This review focused on describing in vivo anti-ageing activity of US-FDA-approved drugs and found that alogliptin, canagliflozin and metformin might produce anti-ageing activity via AMPK activation. Rapamycin and canagliflozin are capable to inhibit mTOR to promote lifespan. Atracurium, carnitine and statins act as DAF-16 activators, which potentially contribute to anti-ageing activity. Hydralazine, lisinopril, rosiglitazone and zidovudine may help stabilize genomic integrity to prolong life expectancy. Other indirect mechanisms, including insulin-lowering effect by acarbose and calcium channel blocking activity by verapamil may also promote longevity. Interestingly, some drugs (i.e., canagliflozin, metformin, rapamycin and acarbose) are likely to demonstrate a lifespan-promoting effect predominantly in male animals. These pre-clinical data might provide mechanistic and phenotypic perspectives to better understand the targets of anti-ageing interventions.
  5. Osman MA, Sugnaseelan S, Panandam JM, Ab Ghani NI
    Ecol Evol, 2020 Oct;10(19):10440-10448.
    PMID: 33072271 DOI: 10.1002/ece3.6699
    The difficulty in differentiating the sex of monomorphic bird species has made molecular sexing an important tool in addressing this problem. This method uses noninvasively collected materials such as feathers and may be advantageous for sexing endangered as well as commercialized bird species. In this study, seven primer sets for sexing birds were screened in Aerodramus fuciphagus using a total of 13 feather samples that were randomly selected from the state of Perak, Malaysia. From the screening analysis, only one primer set (P8/WZ/W) successfully differentiated the sex of A. fuciphagus. PCR amplification produced a single 255-bp DNA fragment for males which was derived from CHD-Z (CHD gene region in the sex chromosome Z), while for the females it produced two fragments (144 and 255 bp). The 144-bp fragment was from CHD-W (CHD gene region in the sex chromosome W). Results from sequencing showed no variations in the base sequences of the CHD-W and CHD-Z amplified fragments within the same sexes, except for one male sample (A23) where at position 166, a base substitution occurred (G → A). Phylogenetic analysis of CHD-W showed that four (Apodiformes; Gruiformes; Passeriformes; and Pelecaniformes) out of the five orders investigated had formed four clear clusters within their orders, including the studied order: Apodiformes. Whereas in CHD-Z, four (Accipitriformes; Columbiformes; Galliformes; and Passeriformes) out of five orders investigated formed four clear clusters within their orders, excluding the studied order. In addition, A. fuciphagus and Apus apus (both Apodiformes) showed less divergence in CHD-W than CHD-Z (0% c.f. 9%). The result suggests that in A. fuciphagus, CHD gene evolution occurred at a higher rate in males (CHD-Z) compared to females (CHD-W). This finding may be useful for further studies on sex ratio and breeding management of A. fuciphagus.
  6. Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Jamal R
    Front Microbiol, 2018;9:767.
    PMID: 29755427 DOI: 10.3389/fmicb.2018.00767
    The human gut holds the densest microbiome ecosystem essential in maintaining a healthy host physiology, whereby disruption of this ecosystem has been linked to the development of colorectal cancer (CRC). The advent of next-generation sequencing technologies such as the 16S rRNA gene sequencing has enabled characterization of the CRC gut microbiome architecture in an affordable and culture-free approach. Nevertheless, the lack of standardization in handling and storage of biospecimens, nucleic acid extraction, 16S rRNA gene primer selection, length, and depth of sequencing and bioinformatics analyses have contributed to discrepancies found in various published studies of this field. Accurate characterization of the CRC microbiome found in different stages of CRC has the potential to be developed into a screening tool in the clinical setting. This mini review aims to concisely compile all available CRC microbiome studies performed till end of 2016 and to suggest standardized protocols that are crucial in developing a gut microbiome screening panel for CRC.
  7. Zaidi NE, Shazali NAH, Leow TC, Osman MA, Ibrahim K, Rahman NMANA
    Biomedicine (Taipei), 2022;12(4):9-19.
    PMID: 36816174 DOI: 10.37796/2211-8039.1381
    Over the last few decades, cancer has been regarded as an independent and self sustaining progression. The earliest hallmarks of cancer comprise of sustaining proliferative signalling, avoiding growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Nonetheless, two emerging hallmarks are being described: aberrant metabolic pathways and evasion of immune destruction. Changes in tumour cell metabolism are not restricted to tumour cells alone; the products of the altered metabolism have a direct impact on the activity of immune cells inside the tumour microenvironment, particularly tumour-associated macrophages (TAMs). The complicated process of cancer growth is orchestrated by metabolic changes dictating the tight mutual connection between these cells. Here, we discuss approaches to exploit the interaction of cancer cells' abnormal metabolic activity and TAMs. We also describe ways to exploit it by reprogramming fatty acid metabolism via TAMs.
  8. Loh HY, Norman BP, Lai KS, Rahman NMANA, Alitheen NBM, Osman MA
    Int J Mol Sci, 2019 Oct 06;20(19).
    PMID: 31590453 DOI: 10.3390/ijms20194940
    MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.
  9. Azizi NF, Kumar MR, Yeap SK, Abdullah JO, Khalid M, Omar AR, et al.
    Foods, 2021 May 27;10(6).
    PMID: 34071977 DOI: 10.3390/foods10061210
    Kefir is a fermented beverage with renowned probiotics that coexist in symbiotic association with other microorganisms in kefir grains. This beverage consumption is associated with a wide array of nutraceutical benefits, including anti-inflammatory, anti-oxidative, anti-cancer, anti-microbial, anti-diabetic, anti-hypertensive, and anti-hypercholesterolemic effects. Moreover, kefir can be adapted into different substrates which allow the production of new functional beverages to provide product diversification. Being safe and inexpensive, there is an immense global interest in kefir's nutritional potential. Due to their promising benefits, kefir and kefir-like products have a great prospect for commercialization. This manuscript reviews the therapeutic aspects of kefir to date, and potential applications of kefir products in the health and food industries, along with the limitations. The literature reviewed here demonstrates that there is a growing demand for kefir as a functional food owing to a number of health-promoting properties.
  10. Nik Abd Rahman NMA, Nurliyana MY, Afiqah MNFNN, Osman MA, Hamid M, Lila MAM
    BMC Complement Altern Med, 2019 Nov 29;19(1):340.
    PMID: 31783838 DOI: 10.1186/s12906-019-2757-4
    BACKGROUND: Clinacanthus nutans Lindau (C. nutans) is a species of in Acanthaceae family and primarily used in South East Asian countries. C. nutans is well known as Sabah snake grass in Malaysia, and its leaves have diverse medicinal potential in conventional applications, including cancer treatments. On the basis of literature search, there is less conclusive evidence of the involvement of phytochemical constituents in breast cancer, in particular, animal tumor models. The current study aimed to determine the antitumor and antioxidant activities of C. nutans extract in 4 T1 tumor-bearing mice.

    METHODS: C. nutans leaves were subjected to methanol extraction and divided into two different concentrations, 200 mg/kg (low-dose) and 1000 mg/kg (high-dose). The antitumor effects of C. nutans extracts were assessed using bone marrow smearing, clonogenic, and splenocyte immunotype analyses. In addition, hematoxylin and eosin, tumor weight and tumor volume profiles also used to indicate apoptosis appearance. Serum cytokine levels were examined using ELISA assay. In addition, nitric oxide assay reflecting antioxidant activity was performed.

    RESULTS: From the results obtained, the methanol extract of C. nutans leaves at 200 mg/kg (P 

  11. Zaidi NE, Shazali NAH, Chor ALT, Osman MA, Ibrahim K, Jaoi-Edward M, et al.
    J Vis Exp, 2019 12 14.
    PMID: 31885381 DOI: 10.3791/60281
    Tumor-associated macrophages (TAMs) have been identified as an important component for tumor growth, invasion, metastasis, and resistance to cancer therapies. However, tumor-associated macrophages can be harmful to the tumor depending on the tumor microenvironment and can reversibly alter their phenotypic characteristics by either antagonizing the cytotoxic activity of immune cells or enhancing anti-tumor response. The molecular actions of macrophages and their interactions with tumor cells (e.g., phagocytosis) have not been extensively studied. Therefore, the interaction between immune cells (M1/M2-subtype TAM) and cancer cells in the tumor microenvironment is now a focus of cancer immunotherapy research. In the present study, a live cell coculture model of induced M1 macrophages and mouse mammary 4T1 carcinoma cells was developed to assess the phagocytic activity of macrophages using a time-lapse video feature using phase-contrast, fluorescent, and differential interference contrast (DIC) microscopy. The present method can observe and document multipoint live-cell imaging of phagocytosis. Phagocytosis of 4T1 cells by M1 macrophages can be observed using fluorescent microscopy before staining 4T1 cells with carboxyfluorescein succinimidyl ester (CFSE). The current publication describes how to coculture macrophages and tumor cells in a single imaging dish, polarize M1 macrophages, and record multipoint events of macrophages engulfing 4T1 cells during 13 h of coculture.
  12. Moo CL, Yang SK, Osman MA, Yuswan MH, Loh JY, Lim WM, et al.
    Pol J Microbiol, 2020;69:1-6.
    PMID: 32162852 DOI: 10.33073/pjm-2020-007
    Natural products such as essential oils (EOs) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms. Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents. This study investigates the antibacterial activity and mechanism of β-caryophyllene, a compound that can be found in various EOs, against Bacillus cereus. The minimum inhibitory concentration of β-caryophyllene against B. cereus was 2.5% (v/v), whereas killing kinetics of β-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours. Zeta-potential measurement in the cells treated with half the minimum inhibitory concentration of β-caryophyllene at 1.25% (v/v) showed an increase in the membrane permeability surface charge to -3.98 mV, compared to untreated cells (-5.46 mV). Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene. Additionally, β-caryophyllene does not interfere with the efflux activity of B. cereus via the ethidium bromide influx/efflux activity. The results revealed that β-caryophyllene was able to alter membrane permeability and integrity of B. cereus, leading to membrane damage and intracellular content leakage, which eventually caused cell death.

    Natural products such as essential oils (EOs) are secondary metabolites that can be obtained from either plant or animal sources or produced by microorganisms. Much attention has been given to exploring the use of secondary metabolites as natural antibacterial agents. This study investigates the antibacterial activity and mechanism of β-caryophyllene, a compound that can be found in various EOs, against Bacillus cereus. The minimum inhibitory concentration of β-caryophyllene against B. cereus was 2.5% (v/v), whereas killing kinetics of β-caryophyllene at minimum inhibitory concentration recorded complete bactericidal activity within 2 hours. Zeta-potential measurement in the cells treated with half the minimum inhibitory concentration of β-caryophyllene at 1.25% (v/v) showed an increase in the membrane permeability surface charge to –3.98 mV, compared to untreated cells (–5.46 mV). Intracellular contents leakage of UV-absorbing materials was detected in the cells treated with β-caryophyllene. Additionally, β-caryophyllene does not interfere with the efflux activity of B. cereus via the ethidium bromide influx/efflux activity. The results revealed that β-caryophyllene was able to alter membrane permeability and integrity of B. cereus, leading to membrane damage and intracellular content leakage, which eventually caused cell death.

  13. Moo CL, Osman MA, Yang SK, Yap WS, Ismail S, Lim SH, et al.
    Sci Rep, 2021 10 21;11(1):20824.
    PMID: 34675255 DOI: 10.1038/s41598-021-00249-y
    Antimicrobial resistance remains one of the most challenging issues that threatens the health of people around the world. Plant-derived natural compounds have received considerable attention for their potential role to mitigate antibiotic resistance. This study was carried out to assess the antimicrobial activity and mode of action of a monoterpene, 1,8-cineol (CN) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Results showed that resazurin microplate assay and time-kill analysis revealed bactericidal effects of CN at 28.83 mg/mL. Zeta potential showed that CN increased the surface charge of bacteria and an increase of outer membrane permeability was also detected. CN was able to cause leakage of proteins and nucleic acids in KPC-KP cells upon exposure to CN and ethidium bromide influx/efflux experiment showed the uptake of ethidium bromide into the cell; this was attributed to membrane damage. CN was also found to induce oxidative stress in CN-treated KPC-KP cells through generation of reactive oxygen species which initiated lipid peroxidation and thus damaging the bacterial cell membrane. Scanning and transmission electron microscopies further confirmed the disruption of bacterial cell membrane and loss of intracellular materials. In this study, we demonstrated that CN induced oxidative stress and membrane damage resulting in KPC-KP cell death.
  14. Zaidi NE, Shazali NAH, Leow TC, Osman MA, Ibrahim K, Cheng WH, et al.
    Cells, 2022 Nov 10;11(22).
    PMID: 36428985 DOI: 10.3390/cells11223556
    Tumour heterogeneity refers to the complexity of cell subpopulations coexisting within the tumour microenvironment (TME), such as proliferating tumour cells, tumour stromal cells and infiltrating immune cells. The bidirectional interactions between cancer and the surrounding microenvironment mark the tumour survival and promotion functions, which allow the cancer cells to become invasive and initiate the metastatic cascade. Importantly, these interactions have been closely associated with metabolic reprogramming, which can modulate the differentiation and functions of immune cells and thus initiate the antitumour response. The purpose of this report is to review the CD36 receptor, a prominent cell receptor in metabolic activity specifically in fatty acid (FA) uptake, for the metabolic symbiosis of cancer-macrophage. In this review, we provide an update on metabolic communication between tumour cells and macrophages, as well as how the immunometabolism indirectly orchestrates the tumour metastasis.
  15. Abdelhafeez AM, Alomari FK, Al Ghashmari HM, Newera A, Alshehri HO, Alzulfi FM, et al.
    Cureus, 2023 Nov;15(11):e49367.
    PMID: 38146556 DOI: 10.7759/cureus.49367
    Objectives This study aimed to investigate the awareness and attitudes towards epidural analgesia (EA) among pregnant women in Taif City, Saudi Arabia. The rationale was to identify potential barriers to the acceptance and use of EA, which is an effective pain management option during labor. Methods We conducted a cross-sectional survey at a single healthcare center in Taif City. The participants, pregnant women visiting the center, were recruited using a convenience sampling method. Data collection was facilitated by a questionnaire distributed through a quick response (QR) code. The questionnaire assessed demographic information, awareness levels, previous exposure to EA, and personal attitudes toward its use during labor. Data analysis focused on quantifying the levels of awareness and identifying patterns in attitudes. Results The results revealed a low level of awareness about EA among the participants, with a significant proportion having never been exposed to it before the survey. Attitudes towards EA were varied, with some expressing openness to its use and others displaying apprehension or resistance, which appeared to be influenced by cultural perceptions and a lack of information. Conclusions The study highlighted a substantial lack of awareness and varied attitudes towards EA among pregnant women in Taif City. Educational interventions are necessary to increase awareness and address cultural misconceptions. The study's limited scope and potential sample bias suggest the need for broader culturally tailored research to inform strategies for improving the acceptance and utilization of labor analgesia.
  16. Aziz MNM, Rahim NFC, Hussin Y, Yeap SK, Masarudin MJ, Mohamad NE, et al.
    Pharmaceuticals (Basel), 2021 Jun 03;14(6).
    PMID: 34204873 DOI: 10.3390/ph14060532
    Osteosarcoma (OS) is a life-threatening malignant bone tumor associated with poor prognosis among children. The survival rate of the patient is still arguably low even with intensive treatment provided, plus with the inherent side effects from the chemotherapy, which gives more unfavorable outcomes. Hence, the search for potent anti-osteosarcoma agent with promising safety profile is still on going. Natural occurring substance like curcumin has gained a lot of attention due to its splendid safety profile as well as it pharmacological advantages such as anti-metastasis and anti-angiogenesis. However, natural curcumin was widely known for its poor cellular uptake, which undermines all potential that it possesses. This prompted the development of synthetically synthesized curcuminoid analog, known as (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2- en-1-one (DK1). In this present study, in vitro scratch assay, transwell migration/invasion assay, HUVEC tube formation assay, and ex vivo rat aortic ring assays were performed in order to investigate the anti-metastatic and anti-angiogenic potential of DK1. For further comprehension of DK1 mechanism on human osteosarcoma cell lines, microarray gene expression analysis, quantitative polymerase chain reaction (qPCR), and proteome profiler were adopted, providing valuable forecast from the expression of important genes and proteins related to metastasis and angiogenesis. Based on the data gathered from the bioassays, DK1 was able to inhibit the metastasis and angiogenesis of human osteosarcoma cell lines by significantly reducing the cell motility, number of migrated and invaded cells as well as the tube formation and micro-vessels sprouting. Additionally, DK1 also has significantly regulated several cancer pathways involved in OS proliferation, metastasis, and angiogenesis such as PI3K/Akt and NF-κB in both U-2 OS and MG-63. Regulation of PI3K/Akt caused up-regulation of genes related to metastasis inhibition, namely, PTEN, FOXO, PLK3, and GADD45A. Meanwhile, NF-κB pathway was regulated by mitigating the expression of NF-κB activator such as IKBKB and IKBKE in MG-63, whilst up-regulating the expression of NF-κB inhibitors such as NFKBIA and NFKBIE in U-2 OS. Finally, DK1 also has successfully hindered the metastatic and angiogenic capability of OS cell lines by down-regulating the expression of pro-metastatic genes and proteins like MMP3, COL11A1, FGF1, Endoglin, uPA, and IGFBP2 in U-2 OS. Whilst for MG-63, the significantly down-regulated oncogenes were Serpin E1, AKT2, VEGF, uPA, PD-ECGF, and Endoglin. These results suggest that curcumin analog DK1 may serve as a potential new anti-osteosarcoma agent due to its anti-metastatic and anti-angiogenic attributes.
  17. Osman MA, Neoh HM, Ab Mutalib NS, Chin SF, Mazlan L, Raja Ali RA, et al.
    Sci Rep, 2021 02 03;11(1):2925.
    PMID: 33536501 DOI: 10.1038/s41598-021-82465-0
    Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.
  18. Hassan H, Othman MF, Abdul Razak HR, Zakaria ZA, Ahmad Saad FF, Osman MA, et al.
    Molecules, 2022 Nov 17;27(22).
    PMID: 36432069 DOI: 10.3390/molecules27227969
    [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.
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