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The quantification of PET-CT radiotracers to determine minimal scan time using quadratic formulation

Said MA, Musarudin M, Zulkaffli NF

Ann Nucl Med, 2020 Dec;34(12):884-891.
PMID: 33141408 DOI: 10.1007/s12149-020-01543-x

OBJECTIVE: 18F is the most extensively used radioisotope in current clinical practices of PET imaging. This selection is based on the several criteria of pure PET radioisotopes with an optimum half-life, and low positron energy that contributes to a smaller positron range. In addition to 18F, other radioisotopes such as 68Ga and 124I are currently gained much attention with the increase in interest in new PET tracers entering the clinical trials. This study aims to determine the minimal scan time per bed position (Tmin) for the 124I and 68Ga based on the quantitative differences in PET imaging of 68Ga and 124I relative to 18F.
METHODS: The European Association of Nuclear Medicine (EANM) procedure guidelines version 2.0 for FDG-PET tumor imaging has adhered for this purpose. A NEMA2012/IEC2008 phantom was filled with tumor to background ratio of 10:1 with the activity concentration of 30 kBq/ml ± 10 and 3 kBq/ml ± 10% for each radioisotope. The phantom was scanned using different acquisition times per bed position (1, 5, 7, 10 and 15 min) to determine the Tmin. The definition of Tmin was performed using an image coefficient of variations (COV) of 15%.
RESULTS: Tmin obtained for 18F, 68Ga and 124I were 3.08, 3.24 and 32.93 min, respectively. Quantitative analyses among 18F, 68Ga and 124I images were performed. Signal-to-noise ratio (SNR), contrast recovery coefficients (CRC), and visibility (VH) are the image quality parameters analysed in this study. Generally, 68Ga and 18F gave better image quality as compared to 124I for all the parameters studied.
CONCLUSION: We have defined Tmin for 18F, 68Ga and 124I SPECT CT imaging based on NEMA2012/IEC2008 phantom imaging. Despite the long scanning time suggested by Tmin, improvement in the image quality is acquired especially for 124I. In clinical practice, the long acquisition time, nevertheless, may cause patient discomfort and motion artifact.

Matched MeSH terms: Fluorine Radioisotopes/chemistry; Gallium Radioisotopes/chemistry; Iodine Radioisotopes/chemistry
Production and first use of 153SmCl3-ion exchange resin capsule formulation for assessing gastrointestinal motility

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.

Matched MeSH terms: Radioisotopes/chemistry*
Fulltext Assessment of Radiation and Heavy Metals Risk due to the Dietary Intake of Marine Fishes (Rastrelliger kanagurta) from the Straits of Malacca

Khandaker MU, Asaduzzaman Kh, Nawi SM, Usman AR, Amin YM, Daar E, et al.

PLoS One, 2015;10(6):e0128790.
PMID: 26075909 DOI: 10.1371/journal.pone.0128790

The environment of the Straits of Malacca receives pollution as a result of various industrial and anthropogenic sources, making systematic studies crucial in determining the prevailing water quality. Present study concerns concentrations of natural radionuclides and heavy metals in marine fish (Rastrelliger kanagurta) collected from the Straits of Malacca, since aquatic stock form an important source of the daily diet of the surrounding populace. Assessment was made of the concentrations of key indicator radionuclides (226Ra, 232Th, 40K) and heavy metals (As, Mn, Fe, Cr, Ni, Zn, Cu, Co, Sr, Al, Hg and Pb) together with various radiation indices linked to the consumption of seafish. The annual effective dose for all detected radionuclides for all study locations has been found to be within UNSCEAR acceptable limits as has the associated life-time cancer risk. The overall contamination of the sampled fish from heavy metals was also found to be within limits of tolerance.

Matched MeSH terms: Radioisotopes/chemistry
Dosimetric characterisation of the optically-stimulated luminescence dosimeter in cobalt-60 high dose rate brachytherapy system

Rejab M, Wong JHD, Jamalludin Z, Jong WL, Malik RA, Wan Ishak WZ, et al.

Australas Phys Eng Sci Med, 2018 Jun;41(2):475-485.
PMID: 29756166 DOI: 10.1007/s13246-018-0647-6

This study investigates the characteristics and application of the optically-stimulated luminescence dosimeter (OSLD) in cobalt-60 high dose rate (HDR) brachytherapy, and compares the results with the dosage produced by the treatment planning system (TPS). The OSLD characteristics comprised linearity, reproducibility, angular dependence, depth dependence, signal depletion, bleaching rate and cumulative dose measurement. A phantom verification exercise was also conducted using the Farmer ionisation chamber and in vivo diodes. The OSLD signal indicated a supralinear response (R2 = 0.9998). It exhibited a depth-independent trend after a steep dose gradient region. The signal depletion per readout was negligible (0.02%), with expected deviation for angular dependence due to off-axis sensitive volume, ranging from 1 to 16%. The residual signal of the OSLDs after 1 day bleached was within 1.5%. The accumulated and bleached OSLD signals had a standard deviation of ± 0.78 and ± 0.18 Gy, respectively. The TPS was found to underestimate the measured doses with deviations of 5% in OSLD, 17% in the Farmer ionisation chamber, and 7 and 8% for bladder and rectal diode probes. Discrepancies can be due to the positional uncertainty in the high-dose gradient. This demonstrates a slight displacement of the organ at risk near the steep dose gradient region will result in a large dose uncertainty. This justifies the importance of in vivo measurements in cobalt-60 HDR brachytherapy.

Matched MeSH terms: Cobalt Radioisotopes/chemistry*
Fulltext Radiosynthesis, Stability, Lipophilicity, and Cellular Uptake Evaluations of [131I]Iodine-α-Mangostin for Breast Cancer Diagnosis and Therapy

Nurhidayah W, Widyasari EM, Daruwati I, Mahendra I, Subroto T, Khairul Ikram NK, et al.

Int J Mol Sci, 2023 May 12;24(10).
PMID: 37240025 DOI: 10.3390/ijms24108678

The high rate of incidence and mortality caused by breast cancer encourage urgent research to immediately develop new diagnostic and therapeutic agents for breast cancer. Alpha mangostin (AM) is a natural compound reported to have anti-breast cancer properties. Its electron-donating groups structure allows it to be labeled with an iodine-131 radioisotope to develop a candidate of a diagnostic and therapeutic agent for breast cancer. This study aims to prepare the [131I]Iodine-α-mangostin ([131I]I-AM) and evaluate its stability, lipophilicity, and cellular uptake in breast cancer cell lines. The [131I]I-AM was prepared by direct radiosynthesis with Chloramine-T method in two conditions (A: AM dissolved in NaOH, B: AM dissolved in ethanol). Reaction time, pH, and mass of the oxidizing agent were optimized as crucial parameters that affected the radiosynthesis reaction. Further analysis was conducted using the radiosynthesis conditions with the highest radiochemical purity (RCP). Stability tests were carried out at three storage conditions, including -20, 2, and 25 °C. A cellular uptake study was performed in T47D (breast cancer cell line) and Vero cells (noncancerous cell line) at various incubation times. The results show that the RCP values of [131I]I-AM under conditions A and B were 90.63 ± 0.44 and 95.17 ± 0.80% (n = 3), respectively. In the stability test, [131I]I-AM has an RCP above 90% after three days of storage at -20 °C. A significant difference was obtained between [131I]I-AM uptake in T47D and Vero cells. Based on these results, [131I]I-AM has been prepared with high RCP, stable at -20 °C, and specifically uptaken by breast cancer cell lines. Biodistribution evaluations in animals are recommended as further research in developing [131I]I-AM as a diagnostic and therapeutic agent for breast cancer.

Matched MeSH terms: Iodine Radioisotopes/chemistry
Fulltext Therapeutic radionuclides in nuclear medicine: current and future prospects

Yeong CH, Cheng MH, Ng KH

J Zhejiang Univ Sci B, 2014 Oct;15(10):845-63.
PMID: 25294374 DOI: 10.1631/jzus.B1400131

The potential use of radionuclides in therapy has been recognized for many decades. A number of radionuclides, such as iodine-131 ((131)I), phosphorous-32 ((32)P), strontium-90 ((90)Sr), and yttrium-90 ((90)Y), have been used successfully for the treatment of many benign and malignant disorders. Recently, the rapid growth of this branch of nuclear medicine has been stimulated by the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain and neuroendocrine and other malignant or non-malignant tumours. Today, the field of radionuclide therapy is enjoying an exciting phase and is poised for greater growth and development in the coming years. For example, in Asia, the high prevalence of thyroid and liver diseases has prompted many novel developments and clinical trials using targeted radionuclide therapy. This paper reviews the characteristics and clinical applications of the commonly available therapeutic radionuclides, as well as the problems and issues involved in translating novel radionuclides into clinical therapies.

Matched MeSH terms: Radioisotopes/chemistry*
Fulltext Optimization of integrated impeller mixer via radiotracer experiments

Othman N, Kamarudin SK, Takriff MS, Rosli MI, Engku Chik EM, Adnan MA

ScientificWorldJournal, 2014;2014:242658.
PMID: 24741344 DOI: 10.1155/2014/242658

Radiotracer experiments are carried out in order to determine the mean residence time (MRT) as well as percentage of dead zone, V dead (%), in an integrated mixer consisting of Rushton and pitched blade turbine (PBT). Conventionally, optimization was performed by varying one parameter and others were held constant (OFAT) which lead to enormous number of experiments. Thus, in this study, a 4-factor 3-level Taguchi L9 orthogonal array was introduced to obtain an accurate optimization of mixing efficiency with minimal number of experiments. This paper describes the optimal conditions of four process parameters, namely, impeller speed, impeller clearance, type of impeller, and sampling time, in obtaining MRT and V dead (%) using radiotracer experiments. The optimum conditions for the experiments were 100 rpm impeller speed, 50 mm impeller clearance, Type A mixer, and 900 s sampling time to reach optimization.

Matched MeSH terms: Radioisotopes/chemistry*
Optimising the Azeotropic Drying of 18F-Fluorine Wayto Improve the 18F-Fluorocholine Radiochemical Yield

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.

Matched MeSH terms: Fluorine Radioisotopes/chemistry*
Analytical GC-FID Method for the Determination of Organic Solvents in Radiopharmaceuticals

Hassan H, Othman MF, Zakaria ZA, Saad FFA, Abdul Razak HR

Curr Radiopharm, 2021;14(2):131-144.
PMID: 33115398 DOI: 10.2174/1874471013999201027215704

BACKGROUND: 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.
OBJECTIVE: 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 samples. The effect of injection holding time, temperature variation in the injection port, and the column temperature on the analysis time and resolution (R ≥ 1.5) of ethanol and acetonitrile was studied extensively.
METHODS: 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.
RESULTS: The proposed analytical method surpassed the acceptance criteria including the linearity > 0.990 (correlation coefficient of R2), 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).
CONCLUSION: The proposed analytical method has been successfully implemented to determine the organic solvent in the [18F]fluoro-ethyl-tyrosine ([18F]FET), [18F]fluoromisonidazole ([18F]FMISO), and [18F]fluorothymidine ([18F]FLT).

Matched MeSH terms: Fluorine Radioisotopes/chemistry*
Fulltext Preparation, Characterization, and Radiolabeling of [68Ga]Ga-NODAGA-Pamidronic Acid: A Potential PET Bone Imaging Agent

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.

Matched MeSH terms: Gallium Radioisotopes/chemistry
Fulltext Synthesis of [18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics

Roselt P, Cullinane C, Noonan W, Elsaidi H, Eu P, Wiebe LI

Molecules, 2020 Dec 03;25(23).
PMID: 33287202 DOI: 10.3390/molecules25235700

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E's biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[18F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([18F]F-γ-T-3) was prepared for this purpose. [18F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [18F]fluoride in DMF/K222. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [18F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [18F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [18F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.

Matched MeSH terms: Fluorine Radioisotopes/chemistry*

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