Impact of total activity variation in 18F-FDG injected with the overall PET image quality in oncology patients

The preliminary study aims to investigate whether variation on dose activity 18F -FDG will influence the overall PET image quality in oncology patients. This is a retrospective analysis of 10 oncology patients who were injected with an average of 337.40 ± 38.43 MBq of 18F -FDG for PET/CT whole body examination. Patients were divided into 2 groups based on total activity of 18F -FDG injected: less than 333 MBq (302.96±12.65 MBq) (group 1) and more than 333 MBq (371.85±14.00 MBq) (group 2). Multiple Image Projection (MIP) PET images were scored visually by two qualified nuclear radiologists using a two-point scoring scale (poor and excellent). The agreement between radiologists was analysed using kappa measure of agreement (K). The prediction on poor-to-excellent PET image by the total activity of 18F-FDG injected was analysed using a Chi-squared test (x 2). A p value of 0.05). Therefore, there is no strong evidence suggest that the dose injected will influence the PET image quality. Hence, it is recommended to use low-dosed of 18F -FDG technique as it also potentially yields a comparable PET image and reduces radiation burden to the patients

Synthesis of fluorine-18-labelled choline (18F-fluorocholine): towards an early and accurate management of prostate cancer in Malaysia

Prostate cancer is ranked fourth among the most prevalent cancers in men in Malaysia. It is anticipated that the number of prostate cancer sufferers’ will increase in future. With the emergence of reputable imaging tracers such as fluorine-18-labelled choline (18F-fluorocholine) and gallium-68 labelled prostate specific membrane antigen (68Ga-PSMA) for the diagnosis of prostate cancer in positron emission tomography / computed tomography (PET/CT) modality, the challenges in the staging and detection accuracy would promise a better management strategy for patients. This article presents the synthesis of 18F-fluorocholine and a convenient method for quality control analysis of 18F-fluorocholine. In addition, the aim of this research work is to assist local Good Manufacturing Practice (GMP) radiopharmaceutical laboratories that routinely produce 18F-fluorodeoxyglucose (18F-FDG), to start producing 18F-fluorocholine as a tracer for prostate cancer imaging

Preparation, characterization, and radiolabeling of [68Ga]Nodaga-pamidronic acid: a potential PET bone imaging agent

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

Development of convenient quality control analysis method and improvement on the radiochemical yield using F-18-Labelled choline

Prostate cancer continues to be the most prevalent cancer in men in Malaysia. It is anticipated that the number of prostate cancer sufferers’ will increase in future. In the case of Positron Emission Tomography / Computed Tomography (PET/CT), clinicians cannot solely rely on F-18 Fluorodeoxyglucose (F-18 FDG) as there were few studies demonstrated the use of F-18 FDG was pointless in prostate cancer imaging. Thus, this current study presents development of convenient quality control analysis method and improvement performed on the azeotropic drying of no-carrier-added (n.c.a.) F-18 Fluorine to increase the F-18 Fluorocholine (F-18 FCH) radiochemical yield. From these studies, a convenient, efficient and reliable method for quality control analysis of F-18 FCH was successfully developed and validated to comply all the release criteria even in a limited equipment set-up. As most of the equipment set-up in the quality control laboratory in the present study was meant for the routine quality control analysis of F-18 FDG, several parameters were changed in order to adapt to the F-18 FCH quality control method without affecting the routine quality control analysis of F-18 FDG. The synthesis of F-18 FCH was successfully performed on a commercial synthesis module, GE TracerLab MxFDG with fairly good radiochemical yields, between 5 to 15%, which decay is not corrected. Interestingly, the finding from this study shows the potential of improvement on the azeotropic drying condition of n.c.a F-18 Fluorine as a preferred technique to improve the radiochemical yield of F-18 FCH

Inconsistency of lesion quantitative assessment in 2D SUV and 3D SUV quantification techniques for [18F]-FDG PET/CT: a phantom study

This study was performed to assess the inconsistency of lesion quantification in standardised uptake value (SUV) [ 18F]-FDG between Ellipse (2-Dimensional) and Ellipsoid (3-Dimensional) quantification techniques by using PET/ CT image quality phantom. Reconstructed images of PET/CT ACR phantom was used to assess the quantification of SUV (SUVmax, SUVavg and SUVmin) on selected regions of interest. Statistical analysis of paired t-test was performed to compare the lesion quantification in SUV [18F]-FDG between 2D and 3D techniques. The quantification techniques were consistently similar of assessment between 2D SUVmax and 3D SUVmax at 12mm of ROI lesion with [(0.00 ± 0.02), t(29)=-0.48, p>0.05]. However, the rest of quantification techniques of 2D SUVmax, 3D SUVmax, 2D SUVavg, 3D SUVavg, 2D SUVmin and 3D SUVmin, results shown significant inconsistency since the p >0.05]. However, the rest of quantification techniques of 2D SUVmax, 3D SUVmax, 2D SUVavg, 3D SUVavg, 2D SUVmin and 3D SUVmin, results shown significant inconsistency since the p<0.05. This phantom study has proven that there were inconsistency of lesion quantitative assessment in 2D SUV and 3D SUV quantification techniques for [18F]-FDG PET/CT

Optimal 18F-fluorination conditions for the high radiochemical yield of [18F]AlF-NOTA-NHS complexes

18F-fluorination using aluminum-fluoride ([18F]AlF) chelate technique has been reported to give a low-to-moderate radiochemical yield, between 5 and 20%. Therefore, the work described here outlines the optimum 18F-fluorination condition for the formation of [18F]AlF2+ and [18F]AlF-NOTA-NHS complex with the radiochemical yield (RCY) and purity (RCP) of more than 90% as a prerequisite step before proceeding with the radiopharmaceutical preparation using the [18F]AlF-bifunctional chelator technique. As well as being simple, the suggested method is practical and relevant for beginners interested in 18F-fluorination with [18F]AlF-chelate complex technique or also for a researcher who aims to proceed on an extensive scale

Assessing the influence of neglected GC-FID variables on the multiple responses using multivariate optimization for the determination of ethanol and acetonitrile in radiopharmaceuticals

Analytical gas chromatography in line with a flame ionization detector (GC-FID) method was developed and validated for direct determination of organic solvents in [18F]fluoro-ethyl-tyrosine ([18F]FET), [18F]fluoromisonidazole ([18F]FMISO) and [18F]fluorothymidine ([18F]FLT). Variables of the splitless time (min) and injection temperature (°C) on the response of analysis time and resolution were optimized with the assistance of a two-level full factorial design and desirability function of Derringer. The proposed procedure was validated following the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) guideline. Excellent linearity, R2 > 0.990, indicated that approximately 99% of the response variance could be predicted from ethanol and acetonitrile concentrations ranging from 0.5 to 6.0 mg mL−1 and 0.1 to 0.8 mg mL−1, respectively. The proposed procedure has proved to be selective, sensitive, and accurate (90–110%), with excellent repeatability and precision (RSD  0.05) and demonstrated that the proposed method was robust for a splitless time of 1.0 ± 0.5 min and an injection temperature of 210 ± 10 °C. The proposed method was also successfully used for the quantitative determination of ethanol and acetonitrile in [18F]FET, [18F]FMISO, and [18F]FLT. Both solvents were well separated (R, 4.1–4.3) within 4.5 min. Therefore, the proposed method is relevant for routine quality control analysis of all 18F-radiopharmaceutical derivatives for the direct determination of ethanol and acetonitrile

Analytical GC-FID method for the determination of organic solvents in radiopharmaceutical

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 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)