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  1. Ng AH, Ng KH, Dharmendra H, Perkins AC
    Appl Radiat Isot, 2009 Oct;67(10):1864-8.
    PMID: 19049851 DOI: 10.1016/j.apradiso.2008.10.010
    A simple sphere test phantom has been developed for routine performance testing of SPECT systems in situations where expensive commercial phantoms may not be available. The phantom was based on a design with six universal syringe hubs set in the frame to support a circular array of six glass blown spheres of different sizes. The frame was then placed into a water-filled CT abdomen phantom and scanned with a triple head camera system (Philips IRIX, USA). Comparison was made with a commercially available phantom (Deluxe Jaszczak phantom). Whereas the commercial phantom demonstrates cold spot resolution, an important advantage of the sphere test phantom was that hot spot resolution could be easily measured using almost half (370MBq) of the activity recommended for use in the commercial phantom. Results showed that the contrast increased non-linearly with sphere volume and radionuclide concentration. The phantom was found to be suitable as an inexpensive option for daily performance tests.
  2. Yeong CH, Ng KH, Abdullah BJJ, Chung LY, Goh KL, Perkins AC
    Appl Radiat Isot, 2014 Dec;94:216-220.
    PMID: 25222875 DOI: 10.1016/j.apradiso.2014.08.009
    Radionuclide imaging using (111)In, (99m)Tc and (153)Sm is commonly undertaken for the clinical investigation of gastric emptying, intestinal motility and whole gut transit. However the documented evidence concerning internal radiation dosimetry for such studies is not readily available. This communication documents the internal radiation dosimetry for whole gastrointestinal transit studies using (111)In, (99m)Tc and (153)Sm labeled formulations. The findings were compared to the diagnostic reference levels recommended by the United Kingdom Administration of Radioactive Substances Advisory Committee, for gastrointestinal transit studies.
  3. Yeong CH, Abdullah BJ, Ng KH, Chung LY, Goh KL, Perkins AC
    Nucl Med Commun, 2013 Jul;34(7):645-51.
    PMID: 23612704 DOI: 10.1097/MNM.0b013e32836141e4
    This paper describes the use of gamma scintigraphic and magnetic resonance (MR) fusion images for improving the anatomical delineation of orally administered radiotracers used in gastrointestinal (GI) transit investigations.
  4. Yeong CH, Blackshaw PE, Ng KH, Abdullah BJ, Blaauw M, Dansereau RJ, et al.
    Appl Radiat Isot, 2011 Sep;69(9):1181-4.
    PMID: 21550260 DOI: 10.1016/j.apradiso.2011.04.017
    Neutron activation of Sm-152 offers a method of radiolabeling for the in vivo study of oral dose formulations by gamma scintigraphy. Reproducibility measurements are needed to ensure the robustness of clinical studies. 204 enteric-coated guaifenesin core tablets (10mg of Sm(2)O(3)) were irradiated by thermal neutrons to achieve 1 MBq at 48 h. Administered activities were 0.86±0.03 MBq. Good reproducibility (CV=3.5%) was observed over 24 weeks ensuring that volunteer doses were within the dose reference level of 0.8 mSv.
  5. Ng AH, Clay D, Blackshaw PE, Bugby SL, Morgan PS, Lees JE, et al.
    Nucl Med Commun, 2015 Nov;36(11):1134-42.
    PMID: 26352214 DOI: 10.1097/MNM.0000000000000377
    To develop a method for the assessment of small field of view (SFOV) gamma cameras using a novel phantom designed to simulate the localization of sentinel nodes in the presence of a high-activity injection site.
  6. Tan HY, Yeong CH, Wong YH, McKenzie M, Kasbollah A, Md Shah MN, et al.
    Nucl Med Biol, 2020 09 30;90-91:55-68.
    PMID: 33039974 DOI: 10.1016/j.nucmedbio.2020.09.005
    Theranostics in nuclear medicine refers to personalized patient management that involves targeted therapy and diagnostic imaging using a single or combination of radionuclide (s). The radionuclides emit both alpha (α) or beta (β-) particles and gamma (γ) rays which possess therapeutic and diagnostic capabilities, respectively. However, the production of these radionuclides often faces difficulties due to high cost, complexity of preparation methods and that the products are often sourced far from the healthcare facilities, hence losing activity due to radioactive decay during transportation. Subject to the availability of a nuclear reactor within an accessible distance from healthcare facilities, neutron activation is the most practical and cost-effective route to produce radionuclides suitable for theranostic purposes. Holmium-166 (166Ho), Lutetium-177 (177Lu), Rhenium-186 (186Re), Rhenium-188 (188Re) and Samarium-153 (153Sm) are some of the most promising neutron-activated radionuclides that are currently in clinical practice and undergoing clinical research for theranostic applications. The aim of this paper is to review the physical characteristics, current clinical applications and future prospects of these neutron activated radionuclides in theranostics. The production, physical properties, validated clinical applications and clinical studies for each neutron-activated radionuclide suitable for theranostic use in nuclear medicine are reviewed in this paper.
  7. Ng AH, Blackshaw PE, Alqahtani MS, Jambi LK, Bugby SL, Lees JE, et al.
    Nucl Med Commun, 2017 Sep;38(9):729-736.
    PMID: 28704342 DOI: 10.1097/MNM.0000000000000715
    INTRODUCTION: Hybrid imaging has proven to be a major innovation in nuclear medicine, allowing the fusion of functional information with anatomical detail. In the past, the use of hybrid imaging such as PET-CT, PET-MRI and SPECT-CT has been of great clinical benefit; however, these scanners are relatively large and bulky. We have developed and investigated the clinical application of a compact small field of view hybrid gamma camera (HGC) that is suitable for small-organ imaging at the patient bedside.

    PATIENTS AND METHODS: The HGC - consisting of a CsI(Tl) scintillation crystal coupled to an electron-multiplying charge-coupled device and an optical camera - was used in this study. Eligible patients attending the nuclear medicine clinic at Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK, were invited to take part in this study. Following the standard injection of either a Tc-labelled or I-labelled radiopharmaceutical, images of the patient were acquired using the HGC and presented in a fused optical-gamma display.

    RESULTS: There were 24 patients enrolled in the study (age range between 30 and 83 years, mean: 58.6 years), images of 18 of whom were successfully acquired. These included patients who were undergoing bone, thyroid, lacrimal drainage, DaTscan and lymphatic imaging. In general, the small field of view system was well suited to small-organ imaging. The uptake could be clearly seen in relation to the patient surface anatomy and showed particular promise for lymphatic, thyroid and lacrimal drainage studies.

    CONCLUSION: This pilot study has demonstrated the first clinical results of hybrid optical-gamma imaging in patients. The use of this system has raised new possibilities for small-organ imaging, in which the localization of radiopharmaceutical uptake can be presented in an anatomical context using optical imaging. The compact nature of the hybrid system offers the potential for bedside investigations and intraoperative use.

  8. Ng AH, Alqahtani MS, Jambi LK, Bugby SL, Lees JE, Perkins AC
    Br J Radiol, 2019 Jun;92(1098):20190020.
    PMID: 30864832 DOI: 10.1259/bjr.20190020
    OBJECTIVE: To examine the imaging capability of a novel small field of view hybrid gamma camera (HGC) using 125I seeds prior to surgical use.

    METHODS: The imaging performance of the camera system was assessed quantitatively and qualitatively at different source depths, source to collimator distances (SCD), activity levels, acquisition times and source separations, utilising bespoke phantoms.

    RESULTS: The system sensitivity and spatial resolution of the HGC for 125I were 0.41 cps/MBq (at SCD 48 mm) and 1.53 ± 0.23 mm (at SCD 10 mm) respectively. The camera was able to detect the 125I seed at a SCD of 63 mm (with no scattering material in place) in images recorded within a 1-min acquisition time. The detection of the seeds beneath scattering material (simulating deep-seated tumours) was limited to depths of less than 20 mm beneath the skin surface with a SCD of 63 mm and seed activity of 2.43 MBq. Subjective assessments of the hybrid images acquired showed the capability of the HGC for localising the 125I seeds.

    CONCLUSION: This preliminary ex vivo study demonstrates that the HGC is capable of detecting 125I seeds and could be a useful tool in radioactive seed localisation with the added benefit of providing hybrid optical γ images for guiding breast conserving surgery.

    ADVANCES IN KNOWLEDGE: The SFOV HGC could provide high resolution fused optical-gamma images of 125I radioactive seeds indicating the potential use in intraoperative surgical procedure such as RSL.

  9. Tan HY, Wong YH, Kasbollah A, Md Shah MN, Perkins AC, Yeong CH
    Nucl Med Commun, 2023 Apr 01;44(4):227-243.
    PMID: 36808108 DOI: 10.1097/MNM.0000000000001665
    Personalised cancer treatment is of growing importance and can be achieved via targeted radionuclide therapy. Radionuclides with theranostic properties are proving to be clinically effective and are widely used because diagnostic imaging and therapy can be accomplished using a single formulation that avoids additional procedures and unnecessary radiation burden to the patient. For diagnostic imaging, single photon emission computed tomography (SPECT) or positron emission tomography (PET) is used to obtain functional information noninvasively by detecting the gamma (γ) rays emitted from the radionuclide. For therapeutics, high linear energy transfer (LET) radiations such as alpha (α), beta (β - ) or Auger electrons are used to kill cancerous cells in close proximity, whereas sparing the normal tissues surrounding the malignant tumour cells. One of the most important factors that lead to the sustainable development of nuclear medicine is the availability of functional radiopharmaceuticals. Nuclear research reactors play a vital role in the production of medical radionuclides for incorporation into clinical radiopharmaceuticals. The disruption of medical radionuclide supplies in recent years has highlighted the importance of ongoing research reactor operation. This article reviews the current status of operational nuclear research reactors in the Asia-Pacific region that have the potential for medical radionuclide production. It also discusses the different types of nuclear research reactors, their operating power, and the effects of thermal neutron flux in producing desirable radionuclides with high specific activity for clinical applications.
  10. Yeong CH, Abdullah BJ, Ng KH, Chung LY, Goh KL, Sarji SA, et al.
    Appl Radiat Isot, 2012 Mar;70(3):450-5.
    PMID: 22178699 DOI: 10.1016/j.apradiso.2011.11.056
    We produced an enteric-coated gelatine capsule containing neutron-activated (153)Sm-labelled resin beads for use in gastrointestinal motility studies. In vitro test in simulated gastrointestinal environment and in vivo study on volunteers were performed. Scintigraphic images were acquired from ten volunteers over 24h while blood and urine samples were collected to monitor the presence of (153)Sm. All the capsules remained intact in stomach. This proved to be a safe and practical oral capsule formulation for whole gut transit scintigraphy.
  11. Yeong CH, Abdullah BJ, Ng KH, Chung LY, Goh KL, Sarji SA, et al.
    Nucl Med Commun, 2011 Dec;32(12):1256-60.
    PMID: 21934547 DOI: 10.1097/MNM.0b013e32834b3ac8
    Nuclear medicine techniques are well established for the investigation of gastrointestinal (GI) motility and transit. Ion-exchange resins radiolabelled with ⁹⁹mTc and ¹¹¹In are widely used as nonabsorbable radiopharmaceutical markers, with ¹¹¹In being preferred for whole-gut transit studies. This radionuclide, however, is not produced in many countries and may be expensive when obtained through international shipment. This study describes the use of neutron-activated ¹⁵³Sm-resin as an alternative tracer for use in GI scintigraphic investigation. A measure of 50 mg of stable samarium-152 chloride (¹⁵²SmCl₃) was incorporated into 100 mg of cation-exchange resin and irradiated in a neutron flux of 1 × 10¹³ cm⁻² s⁻¹ for 100 s to achieve an activity of 5 MBq after 66 h. Aliquots of ¹¹¹In-radiolabelled resin (5 MBq) were prepared for comparison of labelling and stability. Radiolabelling efficiencies were obtained by washing resin with distilled water, and the activity lost was measured. The radiolabelled resins were immersed in simulated gastric and intestinal fluid environments, and the retention of ¹⁵³Sm³⁺ and ¹¹¹In³⁺ was measured over a 24 h period. At 66 h after production, 91.15 ± 12.42% of ¹⁵³Sm was bound to the resin after washing in distilled water, whereas radiolabelling with ¹¹¹In achieved 99.96 ± 0.02% efficiency. Both radiolabelled resins demonstrated almost 100% stability in simulated intestinal fluid and >90% stability in artificial gastric juice over 24 h. The performance of neutron-activated ¹⁵³Sm-resin is similar to that of ¹¹¹In-resin and can be used as an alternative tracer for GI transit studies when In is not available.
  12. Hashikin NA, Yeong CH, Abdullah BJ, Ng KH, Chung LY, Dahalan R, et al.
    PLoS One, 2015;10(9):e0138106.
    PMID: 26382059 DOI: 10.1371/journal.pone.0138106
    Samarium-153 (153Sm) styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (90Y) microspheres in liver radioembolization therapy. Unlike the pure beta emitter 90Y, 153Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post-procedure imaging following therapy.
  13. Hashikin NAA, Yeong CH, Guatelli S, Abdullah BJJ, Ng KH, Malaroda A, et al.
    Phys Med Biol, 2017 Aug 22;62(18):7342-7356.
    PMID: 28686171 DOI: 10.1088/1361-6560/aa7e5b
    We aimed to investigate the validity of the partition model (PM) in estimating the absorbed doses to liver tumour ([Formula: see text]), normal liver tissue ([Formula: see text]) and lungs ([Formula: see text]), when cross-fire irradiations between these compartments are being considered. MIRD-5 phantom incorporated with various treatment parameters, i.e. tumour involvement (TI), tumour-to-normal liver uptake ratio (T/N) and lung shunting (LS), were simulated using the Geant4 Monte Carlo (MC) toolkit. 108track histories were generated for each combination of the three parameters to obtain the absorbed dose per activity uptake in each compartment ([Formula: see text], [Formula: see text], and [Formula: see text]). The administered activities, A were estimated using PM, so as to achieve either limiting doses to normal liver, [Formula: see text] or lungs, [Formula: see text] (70 or 30 Gy, respectively). Using these administered activities, the activity uptake in each compartment ([Formula: see text], [Formula: see text], and [Formula: see text]) was estimated and multiplied with the absorbed dose per activity uptake attained using the MC simulations, to obtain the actual dose received by each compartment. PM overestimated [Formula: see text] by 11.7% in all cases, due to the escaped particles from the lungs. [Formula: see text] and [Formula: see text] by MC were largely affected by T/N, which were not considered by PM due to cross-fire exclusion at the tumour-normal liver boundary. These have resulted in the overestimation of [Formula: see text] by up to 8% and underestimation of [Formula: see text] by as high as  -78%, by PM. When [Formula: see text] was estimated via PM, the MC simulations showed significantly higher [Formula: see text] for cases with higher T/N, and LS  ⩽  10%. All [Formula: see text] and [Formula: see text] by MC were overestimated by PM, thus [Formula: see text] were never exceeded. PM leads to inaccurate dose estimations due to the exclusion of cross-fire irradiation, i.e. between the tumour and normal liver tissue. Caution should be taken for cases with higher TI and T/N, and lower LS, as they contribute to major underestimation of [Formula: see text]. For [Formula: see text], a different correction factor for dose calculation may be used for improved accuracy.
  14. Tan HY, Wong YH, Kasbollah A, Md Shah MN, Abdullah BJJ, Perkins AC, et al.
    Nucl Med Commun, 2022 Apr 01;43(4):410-422.
    PMID: 35045548 DOI: 10.1097/MNM.0000000000001529
    PURPOSE: Hepatic radioembolization is an effective minimally invasive treatment for primary and metastatic liver cancers. Yttrium-90 [90Y]-labelled resin or glass beads are typically used as the radioembolic agent for this treatment; however, these are not readily available in many countries. In this study, novel samarium-153 oxide-loaded polystyrene ([153Sm]Sm2O3-PS) microspheres were developed as a potential alternative to 90Y microspheres for hepatic radioembolization.

    METHODS: The [152Sm]Sm2O3-PS microspheres were synthesized using solid-in-oil-in-water solvent evaporation. The microspheres underwent neutron activation using a 1 MW open-pool research reactor to produce radioactive [153Sm]Sm2O3-PS microspheres via 152Sm(n,γ)153Sm reaction. Physicochemical characterization, gamma spectroscopy and in-vitro radionuclide retention efficiency were carried out to evaluate the properties and stability of the microspheres before and after neutron activation.

    RESULTS: The [153Sm]Sm2O3-PS microspheres achieved specific activity of 5.04 ± 0.52 GBq·g-1 after a 6 h neutron activation. Scanning electron microscopy and particle size analysis showed that the microspheres remained spherical with an average diameter of ~33 μm before and after neutron activation. No long half-life radionuclide and elemental impurities were found in the samples. The radionuclide retention efficiencies of the [153Sm]Sm2O3-PS microspheres at 550 h were 99.64 ± 0.07 and 98.76 ± 1.10% when tested in saline solution and human blood plasma, respectively.

    CONCLUSIONS: A neutron-activated [153Sm]Sm2O3-PS microsphere formulation was successfully developed for potential application as a theranostic agent for liver radioembolization. The microspheres achieved suitable physical properties for radioembolization and demonstrated high radionuclide retention efficiency in saline solution and human blood plasma.

  15. Alregib AH, Tan HY, Wong YH, Kasbollah A, Wong EH, Abdullah BJJ, et al.
    J Labelled Comp Radiopharm, 2023 Aug;66(10):308-320.
    PMID: 37287213 DOI: 10.1002/jlcr.4046
    Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are promising treatments for unresectable liver tumours. Some recent studies suggested that combining TACE and TARE in one treatment course might improve treatment efficacy through synergistic cytotoxicity effects. Nonetheless, current formulations do not facilitate a combination of chemo- and radio-embolic agents in one delivery system. Therefore, this study aimed to synthesise a hybrid biodegradable microsphere loaded with both radioactive agent, samarium-153 (153 Sm) and chemotherapeutic drug, doxorubicin (Dox) for potential radio-chemoembolization of advanced liver tumours. 152 Sm and Dox-loaded polyhydroxybutyrate-co-3-hydroxyvalerate (PHBV) microspheres were prepared using water-in-oil-in-water solvent evaporation method. The microspheres were then sent for neutron activation in a neutron flux of 2 × 1012  n/cm2 /s. The physicochemical properties, radioactivity, radionuclide purity, 153 Sm retention efficiency, and Dox release profile of the Dox-153 Sm-PHBV microspheres were analysed. In addition, in vitro cytotoxicity of the formulation was tested using MTT assay on HepG2 cell line at 24 and 72 h. The mean diameter of the Dox-153 Sm-PHBV microspheres was 30.08 ± 2.79 μm. The specific radioactivity was 8.68 ± 0.17 GBq/g, or 177.69 Bq per microsphere. The 153 Sm retention efficiency was more than 99%, tested in phosphate-buffered saline (PBS) and human blood plasma over 26 days. The cumulative release of Dox from the microspheres after 41 days was 65.21 ± 1.96% and 29.96 ± 0.03% in PBS solution of pH 7.4 and pH 5.5, respectively. The Dox-153 Sm-PHBV microspheres achieved a greater in vitro cytotoxicity effect on HepG2 cells (85.73 ± 3.63%) than 153 Sm-PHBV (70.03 ± 5.61%) and Dox-PHBV (74.06 ± 0.78%) microspheres at 300 μg/mL at 72 h. In conclusion, a novel biodegradable microspheres formulation loaded with chemotherapeutic drug (Dox) and radioactive agent (153 Sm) was successfully developed in this study. The formulation fulfilled all the desired physicochemical properties of a chemo-radioembolic agent and achieved better in vitro cytotoxicity on HepG2 cells. Further investigations are needed to evaluate the biosafety, radiation dosimetry, and synergetic anticancer properties of the formulation.
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