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  1. Ahmad Saad FF, Zakaria MH, Appanna B
    J Int Med Res, 2018 Aug;46(8):3138-3148.
    PMID: 29781364 DOI: 10.1177/0300060518773019
    Objectives 18F-choline is a useful tracer for detecting tumours with high lipogenesis. Knowledge of its biodistribution pattern is essential to recognise physiological variants. The aim of this study was to describe the physiologic distribution of 18F-choline and pitfalls in patients with breast cancer. Methods Twenty-one consecutive patients with breast cancer (10 premenopausal and 11 postmenopausal women; mean age, 52.82 ± 10.71 years) underwent 18F-choline positron emission tomography (PET)/computed tomography (CT) for staging. Whole-body PET/CT was acquired after 40 minutes of 18F-choline uptake. Acquired PET images were measured semiquantitatively. Results All patients showed pitfalls unrelated to breast cancer. These findings were predominantly caused by physiological glandular uptake in the liver, spleen, pancreas, bowels, axial skeleton (85%-100%), inflammation and benign changes (4.76%), appendicular skeleton (4.76%-19.049%), and site contamination (61.9%). In <1%, a concomitant metastatic neoplasm was found. The breast showed higher physiological uptake in premenopausal compared with postmenopausal woman (18F-choline maximum standardised uptake values [g/dL] of the right breast = 2.04 ± 0.404 vs 1.59 ± 0.97 and left breast = 2.00 ± 0.56 vs 1.93 ± 1.28, respectively). Conclusion 18F-choline uptake was higher in premenopausal women. Physiological 18F-choline uptake was observed in many sites, representing possible pathologies.
  2. Zakaria MH, Shaharudin S, Ahmad Saad FF
    Eurasian J Med, 2024 Apr 18;56(2):78-85.
    PMID: 39145500 DOI: 10.5152/eurasianjmed.2024.23047
    The utility of the [18]F fluorodeoxyglucose positron emission tomography-computed tomography ([18]F FDG PET-CT) marker for breast cancer is well established. Given its limitations in localizing FDG-negative malignant tumors, the expression of [18]F-fluorocholine ([18]-FCH) may potentially be helpful to improve the overall accuracy in evaluating breast cancer. This study determined the potential of [18]- FCH PET CT as a potential marker in assessing breast cancer phenotypes. We recruited consecutive patients with biopsy-proven breast carcinoma who underwent [18] F-FCH PET-CT following the [18]F-FDG PET-CT imaging. The subjects were dichotomized into human epidermal growth factor receptor 2 (HER2)-negative and HER2-positive genotypes. The maximum standardized uptake value (SUVmax; g/dL) was used to predict the two groups of variables. Global health status (GHS) score based on the EORTC quality of life questionnaire (QLQ) was used to evaluate the outcome of the cohort subjects at 6, 12, and 24 months. There were 21 females with a mean age of 54.48 ± 12.17 years. Eighteen patients had invasive ductal carcinoma (18/21;85.8%) on histology, with 11 (52.4%) were HER2-negative genotype. There was higher sensitivity and specificity of [18]-FCH-PET/CT in breast lesions at 40% and 68.8% compared to [18]FDGPET/CT with 33.3% and 66.7%, respectively. There were significant differences between [18]F-FCH SUVmax (g/dL) of the HER-negative as compared to the HER2- positive group (1.99 g/dL vs. 0.2 g/dL; P < .05). High SUVmax (g/dL) of [18]F-FCH had predicted the HER-negative genotype at the cutoff value of 0.75 (P < .05). High [18]F-FCH showed significantly poor scoring of GHS parameters compared to low FCH at 6 months (mean SUVmax 8.06 vs. 5.40 respectively; P < .05). [18]F-FCH PET-CT is a potential marker in localizing and predicting aggressive breast carcinoma phenotypes.
  3. Tan TH, Hussein Z, Saad FF, Shuaib IL
    Nucl Med Mol Imaging, 2015 Jun;49(2):143-51.
    PMID: 26085860 DOI: 10.1007/s13139-015-0331-7
    To evaluate the diagnostic performance of (68)Ga-DOTATATE (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT), (18)F-FDG PET/CT and (131)I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.
  4. Ahmad Saad FF, Abdul Rashid AM, Md Noh MSF
    J Pancreat Cancer, 2017;3(1):66-70.
    PMID: 30631845 DOI: 10.1089/pancan.2017.0014
    Background: Pancreatic malignancies encompass a heterogenous group of disorders, with poor prognosis at diagnosis. Traditionally, conventional computed tomography (CT) has been used for diagnosis, staging, and follow up. However, this technique lacks functional information; and is limited in diagnosis of occult pancreatic disease. Hybrid imaging in the form of positron emission tomography (PET)/CT provides a potential avenue for early detection and subsequent appropriate therapy. Case Presentation: A 60-year-old male, with a history of abdominal aortic aneurysm which was repaired, came with a complaint of 2 months history of back pain, radiating to the front. The pain was relieved on leaning forward, and aggravated by lying on his back. CT angiography of the abdomen was done, which revealed a concealed aortic aneurysm and a significant atrophy of the pancreatic tail. The serum cancer antigen (CA) 19-9 was elevated (50.0 U/mL, reference range 0.0-37.0 U/mL). At this juncture, the PET scan done revealed no discernible abnormalities. Patient was put on close follow-up in view of the rising trend of CA 19-9 levels. Three months following the initial scans, a repeat 18F-FDG (fluorine 18 fluorodeoxyglucose) PET/CT revealed an FDG-avid lesion at the neck of the pancreas on PET without perceptible changes on the correlated CT. A Whipple's procedure ensued, with histopathological examination findings of pancreatic adenocarcinoma. Conclusion: This article discusses the role of PET/CT in the early diagnosis of inconspicuous pancreatic lesions; which could have averted immediate medical therapy.
  5. Usman MS, Hussein MZ, Fakurazi S, Ahmad Saad FF
    Chem Cent J, 2017 May 30;11(1):47.
    PMID: 29086824 DOI: 10.1186/s13065-017-0275-3
    Gadolinium (Gd)-based contrasts remain one of the most accepted contrast agents for magnetic resonance imaging, which is among the world most recognized noninvasive techniques employed in clinical diagnosis of patients. At ionic state, Gd is considered toxic but less toxic in chelate form. A variety of nano-carriers, including gadolinium oxide (Gd2O3) nanoparticles have been used by researchers to improve the T1 and T2 contrasts of MR images. Even more recently, a few researchers have tried to incorporate contrast agents simultaneously with therapeutic agents using single nano-carrier for theranostic applications. The benefit of this concept is to deliver the drugs, such as anticancer drugs and at the same time to observe what happens to the cancerous cells. The delivery of both agents occurs concurrently. In addition, the toxicity of the anticancer drugs as well as the contrast agents will be significantly reduced due to the presence of the nano-carriers. The use of graphene oxide (GO) and layered double hydroxides (LDH) as candidates for this purpose is the subject of current research, due to their low toxicity and biocompatibility, which have the capacity to be used in theranostic researches. We review here, some of the key features of LDH and GO for simultaneous drugs and diagnostic agents delivery systems for use in theranostics applications.
  6. Hassan H, Abu Bakar S, Halim KN, Idris J, Ahmad Saad FF, Nordin AJ
    J Labelled Comp Radiopharm, 2015 Sep-Oct;58(11-12):458-9.
    PMID: 26395258 DOI: 10.1002/jlcr.3347
    (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.
  7. Hassan H, Bakar SA, Halim KN, Idris J, Saad FF, Nordin AJ
    Curr Radiopharm, 2016;9(2):121-7.
    PMID: 26239237
    BACKGROUND AND OBJECTIVE: 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.

    METHODS: 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.

    RESULTS: From the paired sample 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.

    CONCLUSION: 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.

  8. Mahmud MH, Nordin AJ, Ahmad Saad FF, Azman AZ
    Quant Imaging Med Surg, 2015 Oct;5(5):700-7.
    PMID: 26682140 DOI: 10.3978/j.issn.2223-4292.2015.05.02
    Increased metabolic activity of fluorodeoxyglucose (FDG) in tissue is not only resulting of pathological uptake, but due to physiological uptake as well. This study aimed to determine the impacts of biological and procedural factors on FDG uptake of liver in whole body positron emission tomography/computed tomography (PET/CT) imaging.
  9. Hanafi MH, Mohd Noor N, Ahmad Saad FF, Ramli SH, Mohamed F, Musarudin M
    Med J Malaysia, 2021 07;76(4):551-561.
    PMID: 34305117
    INTRODUCTION: There has already been a rising demand in utilising phantom for hybrid Positron Emission Tomography/ Computed Tomography (PET/CT) scanner of nuclear imaging. This review further clarifies this topic and investigates how the previous research phantoms operated with the need for quantitative hybrid nuclear imaging of PET/CT while providing a relatively high image quality when it was performed. In this article, the necessity of previous and current phantom studies in hybrid nuclear imaging of PET/CT scanners is reviewed.

    METHODS: PubMed and Google Scholar were systematically searched for the relevant studies by following the PRISMA 2009 checklist. A past decade literature search was conducted from 2010 until November 2020 to secure the relevance of the phantom study. Databases were recruited using keywords such as phantom, quantification, standardisation, harmonisation, image quality, standardised uptake value and multicentre study. However, all keywords were related to PET/CT. All abstracts and eligible full-text articles were screened independently, and finally, the quality assessments of this review were performed.

    RESULTS: From the 200 retrieved articles, 80 were rejected after the screening of the abstracts and 35 after reading the full-text. The 20 accepted articles addressed the distribution of phantom types used in selected articles studies which were NEMA (67%), ACR (8%) and others (25%). The articles showed the various experimental studies, either phantom studies (35%) or phantom plus clinical studies (65%). For clinical studies (n = 829), the distribution of prospective studies was (n = 674) and retrospective studies was (n =155). The distribution of phantom pathway application showed the studies focused on 40% of reconstruction protocol studies, 30% of the multicentre and standardisation of accreditation program studies, and 30% of the quantification of uptake values studies.

    CONCLUSIONS: According to this review, the phantom study have a pivotal role in hybrid nuclear imaging of PET/CT either in technical aspects of the scanners (such as data acquisition and reconstruction protocol) or clinical characteristics of patients. In addition to this, the necessity to identify the suitable system phantoms to use within PET/CT scans by considering the continuous development of new phantom studies are needed. Researchers are encouraged to adopt efforts on phantom quantitative validation, including verification with clinical data of patients.

  10. Waeleh N, Saripan MI, Musarudin M, Mashohor S, Ahmad Saad FF
    Appl Radiat Isot, 2021 Oct;176:109885.
    PMID: 34385090 DOI: 10.1016/j.apradiso.2021.109885
    The present study was conducted to determine quantitatively the correlation between injected radiotracer and signal-to-noise ratio (SNR) based on differences in physiques and stages of cancer. Eight different activities were evaluated with modelled National Electrical Manufacturers Association (NEMA) of the International Electrotechnical Commission (IEC) PET's phantom with nine different tumour-to-background ratio (TBR). The findings suggest that the optimal value of dosage is required for all categories of patients in the early stages of cancer diagnosis.
  11. Sani Usman M, Hussein MZ, Fakurazi S, Masarudin MJ, Ahmad Saad FF
    Nanomaterials (Basel), 2017 Aug 31;7(9).
    PMID: 28858229 DOI: 10.3390/nano7090244
    We have developed gadolinium-based theranostic nanoparticles for co-delivery of drug and magnetic resonance imaging (MRI) contrast agent using Zn/Al-layered double hydroxide as the nanocarrier platform, a naturally occurring phenolic compound, gallic acid (GA) as therapeutic agent, and Gd(NO₃)₃ as diagnostic agent. Gold nanoparticles (AuNPs) were grown on the system to support the contrast for MRI imaging. The nanoparticles were characterized using techniques such as Hi-TEM, XRD, ICP-ES. Kinetic release study of the GA from the nanoparticles showed about 70% of GA was released over a period of 72 h. The in vitro cell viability test for the nanoparticles showed relatively low toxicity to human cell lines (3T3) and improved toxicity on cancerous cell lines (HepG2). A preliminary contrast property test of the nanoparticles, tested on a 3 Tesla MRI machine at various concentrations of GAGZAu and water (as a reference) indicates that the nanoparticles have a promising dual diagnostic and therapeutic features to further develop a better future for clinical remedy for cancer treatment.
  12. Usman MS, Hussein MZ, Kura AU, Fakurazi S, Masarudin MJ, Ahmad Saad FF
    Molecules, 2018 Feb 24;23(2).
    PMID: 29495251 DOI: 10.3390/molecules23020500
    We have synthesized a graphene oxide (GO)-based theranostic nanodelivery system (GOTS) for magnetic resonance imaging (MRI) using naturally occurring protocatechuic acid (PA) as an anticancer agent and gadolinium (III) nitrate hexahydrate (Gd) as the starting material for a contrast agent,. Gold nanoparticles (AuNPs) were subsequently used as second diagnostic agent. The GO nanosheets were first prepared from graphite via the improved Hummer's protocol. The conjugation of the GO and the PA was done via hydrogen bonding and π-π stacking interactions, followed by surface adsorption of the AuNPs through electrostatic interactions. GAGPA is the name given to the nanocomposite obtained from Gd and PA conjugation. However, after coating with AuNPs, the name was modified to GAGPAu. The physicochemical properties of the GAGPA and GAGPAu nanohybrids were studied using various characterization techniques. The results from the analyses confirmed the formation of the GOTS. The powder X-ray diffraction (PXRD) results showed the diffractive patterns for pure GO nanolayers, which changed after subsequent conjugation of the Gd and PA. The AuNPs patterns were also recorded after surface adsorption. Cytotoxicity and magnetic resonance imaging (MRI) contrast tests were also carried out on the developed GOTS. The GAGPAu was significantly cytotoxic to the human liver hepatocellular carcinoma cell line (HepG2) but nontoxic to the standard fibroblast cell line (3T3). The GAGPAu also appeared to possess higher T1 contrast compared to the pure Gd and water reference. The GOTS has good prospects of serving as future theranostic platform for cancer chemotherapy and diagnosis.
  13. Usman MS, Hussein MZ, Fakurazi S, Masarudin MJ, Ahmad Saad FF
    PLoS One, 2018;13(7):e0200760.
    PMID: 30044841 DOI: 10.1371/journal.pone.0200760
    We have synthesized a bimodal theranostic nanodelivery system (BIT) that is based on graphene oxide (GO) and composed of a natural chemotherapeutic agent, chlorogenic acid (CA) used as the anticancer agent, while gadolinium (Gd) and gold nanoparticles (AuNPs) were used as contrast agents for magnetic resonance imaging (MRI) modality. The CA and Gd guest agents were simultaneously loaded on the GO nanolayers using chemical interactions, such as hydrogen bonding and π-π non-covalent interactions to form GOGCA nanocomposite. Subsequently, the AuNPs were doped on the surface of the GOGCA by means of electrostatic interactions, which resulted in the BIT. The physico-chemical studies of the BIT affirmed its successful development. The X-ray diffractograms (XRD) collected of the various stages of BIT synthesis showed the successive development of the hybrid system, while 90% of the chlorogenic acid was released in phosphate buffer solution (PBS) at pH 4.8. This was further reaffirmed by the in vitro evaluations, which showed stunted HepG2 cancer cells growth against the above 90% cell growth in the control cells. A reverse case was recorded for the 3T3 normal cells. Further, the acquired T1-weighted image of the BIT doped samples obtained from the MRI indicated contrast enhancement in comparison with the plain Gd and water references. The abovementioned results portray our BIT as a promising future chemotherapeutic for anticancer treatment with diagnostic modalities.
  14. Hassan H, Othman MF, Ashhar ZN, Abdul Razak HR, Ahmad Saad FF
    Malays J Med Sci, 2024 Aug;31(4):213-217.
    PMID: 39247120 DOI: 10.21315/mjms2024.31.4.17
    Prostate-specific membrane antigen (PSMA) has proven to be an important target for diagnostic imaging in prostate cancer. As PSMA is overexpressed on the surface of prostate cancer cells, numerous targeted PSMA ligands have been developed. The emergence of PSMA targeting based on small molecules, such as the PSMA-11 ligand (or PSMA-HBED-CC), has led to breakthroughs, such as [68Ga]Ga-PSMA-11, for positron emission tomography (PET) imaging of biochemically recurrent or metastatic castration-resistant prostate cancer (mCRPC). In addition, the recent approval of [177Lu]Lu-PSMA-617 for the treatment of adult patients with PSMA-positive mCRPC represents an important milestone in prostate cancer therapy. These advances underscore the growing confidence in the use of PSMA-targeted radiopharmaceuticals for the diagnosis and treatment of prostate cancer patients. PSMA-targeted radiopharmaceuticals have been shown to significantly impact treatment planning and clinical decision-making and facilitate the customisation of treatment regimens.
  15. Ashhar Z, Yusof NA, Ahmad Saad FF, Mohd Nor SM, Mohammad F, Bahrin Wan Kamal WH, et al.
    Molecules, 2020 Jun 09;25(11).
    PMID: 32526838 DOI: 10.3390/molecules25112668
    Early diagnosis of bone metastases is crucial to prevent skeletal-related events, and for that, the non-invasive techniques to diagnose bone metastases that make use of image-guided radiopharmaceuticals are being employed as an alternative to traditional biopsies. Hence, in the present work, we tested the efficacy of a gallium-68 (68Ga)-based compound as a radiopharmaceutical agent towards the bone imaging in positron emitting tomography (PET). For that, we prepared, thoroughly characterized, and radiolabeled [68Ga]Ga-NODAGA-pamidronic acid radiopharmaceutical, a 68Ga precursor for PET bone cancer imaging applications. The preparation of NODAGA-pamidronic acid was performed via the N-Hydroxysuccinimide (NHS) ester strategy and was characterized using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (MSn). The unreacted NODAGA chelator was separated using the ion-suppression reverse phase-high performance liquid chromatography (RP-HPLC) method, and the freeze-dried NODAGA-pamidronic acid was radiolabeled with 68Ga. The radiolabeling condition was found to be most optimum at a pH ranging from 4 to 4.5 and a temperature of above 60 °C. From previous work, we found that the pamidronic acid itself has a good bone binding affinity. Moreover, from the analysis of the results, the ionic structure of radiolabeled [68Ga]Ga-NODAGA-pamidronic acid has the ability to improve the blood clearance and may exert good renal excretion, enhance the bone-to-background ratio, and consequently the final image quality. This was reflected by both the in vitro bone binding assay and in vivo animal biodistribution presented in this research.
  16. 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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