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Fulltext Preparation, Optimisation, and In Vitro Evaluation of [18F]AlF-NOTA-Pamidronic Acid for Bone Imaging PET

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.

Matched MeSH terms: Fluorine Radioisotopes*
Correlation between 18F-FDG dosage and SNR on various BMI patient groups tested in NEMA IEC PET phantom

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.

Matched MeSH terms: Fluorine Radioisotopes/administration & dosage*
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/analysis; Fluorine Radioisotopes/chemistry*
18F-labeled Bisphosphonate as an Alternative Candidate to the Gold Standard[18F]sodium fluoride ([18F]NaF) for PET Bone Imaging

Hassan H, Othman MF, Razak HRA

Curr Med Imaging, 2021;17(11):1271-1275.
PMID: 33593263 DOI: 10.2174/1573405617666210216091202

Bone metastases are a common source of malignancy in the skeleton and occur much more often than primary bone cancer. Several works were being performed to identify early markers for bone metastasis and novel drug targets to improve patients' quality of life. As some concerns exist with the [18F]sodiumfluoridein positron emission tomography (PET) bone imaging, there has been an increase in the number of targeted radiopharmaceutical markers for bone metastases imaging in its competitor, 68Ga. Since 18F properties are superior to those of 68Ga, there is a distinct motivation for developing 18F radiopharmaceuticals for bone metastases imaging.

Matched MeSH terms: Fluorine Radioisotopes
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*
Textitis as Seen on 18F-NaF Imaging Using an Ultra-High-Resolution Positron Emission Mammography Scanner

Usmani S, Rasheed R, Al Kandari F

J Nucl Med Technol, 2020 Jun;48(2):181-183.
PMID: 32111663 DOI: 10.2967/jnmt.119.235986

Textitis is a new term used to refer to the degenerative-strain osteoarthritis that comes from excessive use of a smart phone. 18F-NaF is increasingly used in diagnosing skeletal pain that is not identified on radiographs. We report a case of a 26-y-old woman with left breast cancer referred for 18F-NaF PET/CT, who was complaining of right thumb and wrist pain. Findings were negative for bone secondaries. Dedicated hands views were acquired on a positron emission mammography scanner and showed focal uptake at the first carpometacarpal and second metacarpophalangeal joints. On the basis of the strong history, the findings were likely due to active arthritic changes caused by repetitive strain injury from excessive text messaging.

Matched MeSH terms: Fluorine Radioisotopes*
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/pharmacokinetics; Fluorine Radioisotopes/chemistry*
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
18F-PSMA-1007 PET/CT for Initial Staging of Renal Cell Carcinoma in an End-Stage Renal Disease Patient

Marafi F, Sasikumar A, Aldaas M, Esmail A

Clin Nucl Med, 2021 Jan;46(1):e65-e67.
PMID: 33181733 DOI: 10.1097/RLU.0000000000003354

A 46-year-old man with end-stage renal disease and renal cell carcinoma underwent F-FDG PET/CT for initial staging followed by F-PSMA-1007 PET/CT. Unlike F-FDG, which undergoes renal clearance, F-PSMA-1007 undergoes hepatobiliary clearance and thus generates superior quality images. F-PSMA-1007 PET/CT showed intense tracer-avid left renal mass lesion (FDG nonavid); lytic bone lesions (FDG avid) and single liver lesion (FDG nonavid). This case highlights the superiority of F-PSMA-1007 over F-FDG PET/CT in identifying primary lesion as well as metastatic sites in case of renal cell carcinoma even in the presence of end-stage renal disease.

Matched MeSH terms: Fluorine Radioisotopes