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![Figure 9. The MS n and the chromatogram of the NODPAM ([M − H] − m/z...](publication/342054460/figure/fig1/AS:903917193932802@1592522061749/The-MS-n-and-the-chromatogram-of-the-NODPAM-M-H-m-z-59115-RT-1571-min_Q320.jpg)
![Figure 15. In vitro % bone binding assay for [ 99m Tc]Tc-MDP, [ 68...](publication/342054460/figure/fig2/AS:903917193940992@1592522061814/In-vitro-bone-binding-assay-for-99m-TcTc-MDP-68-GaGa-NODPAM-and-68_Q320.jpg)
![Figure 16. In vivo animal biodistribution of [ 68 Ga]Ga-NODPAM in...](publication/342054460/figure/fig3/AS:903917193928704@1592522061895/In-vivo-animal-biodistribution-of-68-GaGa-NODPAM-in-healthy-Sprague-Dawley-rats_Q320.jpg)
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 compo...
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... preparation of NODPAM involves conjugation via the NHS ester strategy [14]. The pamidronic acid:NODAGA-NHS ratio was prepared according to Table 1. The weighed pamidronic acid was diluted with 665 μL of deionized water, and to it, 34 μL of TEA was added to adjust the pH to 8 and then vortexed until it dissolved entirely. ...Context 2
... preparation of NODPAM involves conjugation via the NHS ester strategy [14]. The pamidronic acid:NODAGA-NHS ratio was prepared according to Table 1. The weighed pamidronic acid was diluted with 665 μL of deionized water, and to it, 34 μL of TEA was added to adjust the pH to 8 and then vortexed until it dissolved entirely. ...Context 3
... preparation of NODPAM involves conjugation via the NHS ester strategy [14]. The pamidronic acid:NODAGA-NHS ratio was prepared according to Table 1. The weighed pamidronic acid was diluted with 665 µL of deionized water, and to it, 34 µL of TEA was added to adjust the pH to 8 and then vortexed until it dissolved entirely. ...Citations
... In particular, SPECT can be advantageous for measuring the reserve of myocardial blood flow, diagnosis of multivessel diseases, and quantitative assessment of the kidneys, brain, lungs, and other organs. Moreover, activity quantitation plays a leading role in targeted radionuclide therapies, specifically in personalized medicine [2]. ...
Absolute quantification of Iodine-131 (131I) on Single Photon Emission Computed Tomography (SPECT) imaging is extremely necessary for the lesion dose per administrative differentiated thyroid cancer procedure. However, non-quantitative SPECT imaging makes determining the dose required for a tumour to be treated is challenging. This multi-vendor and multi-centre research uses phantom measures to assess the quantitative accuracy and inter-system variability of various SPECT/CT systems. Hence, this study aims to determine the calibration factor (CF) for 131I activity quantification using the National Electrical Manufacturer Association (NEMA) phantom uptake for the Philips BrightView XCT modality. The accuracy activity concentration for a non-spherical targeted volume is less than 15% compared to a spherical targeted volume (<9%). Furthermore, the CF has no significant difference in the value between the matrix sizes of 64×64, 128×128, and 256×256. Therefore, the gamma camera CF must be precisely determined to convert the reconstructed images' counts into activity values for quantitative imaging. However, the NEMA phantom with spherical geometrical is the standard tool for determining CF, the various geometrical shapes other than spherical should be considered for determining CF because the effect of photon distribution contribution is different for any different lesion geometrical.
... The small molecule PSMA inhibitors is being radiolabel with various metal radioisotopes such as [ 68 [6,7] and one PSMAbased radioligand that is PSMA-617 to be radiolabel with [ 177 Lu]Lutetium for therapeutic purposes [8]. The radiolabeling of these radiometal isotopes with PSMA-11 and PMSA-617 follows a simple coordination complex which favors the formation of stable complex with the bifunctional chelators such as HBED and DOTA [9]. The [ 68 Ge/ 68 Ga] radionuclide generator provides an excellent source of positron-emitting [ 68 Ga]Gallium isotopes without needing an onsite cyclotron. ...
... The radiolabeling of [ 68 Ga]Ga-PSMA-11 is highly pH, temperature, and time-dependent [9,12]. These parameters were investigated with a constant radiolabeling temperature and time of 90 o C and 10 minutes, respectively. ...
... A Scopus search shows that the number of publications on 68 Ga has exponentially increased from 2000 to 2021 ( Figure 1A). Interest in 68 Ga radiopharmaceuticals further came into the limelight with the introduction of radiopharmaceuticals for neuroendocrine tumor imaging (NET), i.e., [ 68 Ga]Ga-DOTA-TOC, [ 68 Ga]Ga-DOTA-NOC, and [ 68 Ga]Ga-DOTA-TATE [1][2][3][4][5]. 68 Ga-DOTA-TATE was approved by the United States Food and Drug Administration (USFDA) in 2016 [6], followed by 68 Ga-DOTA-TOC in 2019 [7]. ...
Designing and implementing various radionuclide production methods guarantees a sustainable supply, which is important for medical use. The use of medical cyclotrons for radiometal production can increase the availability of gallium-68 (68Ga) radiopharmaceuticals. Although generators have greatly influenced the demand for 68Ga radiopharmaceuticals, the use of medical cyclotrons is currently being explored. The resulting 68Ga production is several times higher than obtained from a generator. Moreover, the use of solid targets yields end of purification and end of synthesis (EOS) of up to 194 GBq and 72 GBq, respectively. Furthermore, experiments employing liquid targets have provided promising results, with an EOS of 3 GBq for [68Ga]Ga-PSMA-11. However, some processes can be further optimized, specifically purification, to achieve high 68Ga recovery and apparent molar activity. In the future, 68Ga will probably remain one of the most in-demand radionuclides; however, careful consideration is needed regarding how to reduce the production costs. Thus, this review aimed to discuss the production of 68Ga radiopharmaceuticals using Advanced Cyclotron Systems, Inc. (ACSI, Richmond, BC, Canada) Richmond, Canada and GE Healthcare, Wisconsin, USA cyclotrons, its related factors, and regulatory concerns.
... Statistical analysis of the one-way ANOVA revealed that the difference in the percentage binding of HA was insignificant for all three agents (p > 0.05). The results showed that a higher HA binding assay of more than 90% was achieved with the 18 F derivative than when the 68 Ga derivatives were used [23,27,[56][57][58]. The in vitro HA binding assay recorded the highest value of 91% only with 68 Ga-DOTA-pamidronic acid, while the majority ranged from 70 to 85%. ...
[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.
Skeletal-related events due to bone metastases can be prevented by early diagnosis using radiological or nuclear imaging techniques. Nuclear medicine techniques such as Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) have been used for diagnostic imaging of bone for decades. Although it is widely recognized that conventional diagnostic imaging techniques such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) have high sensitivity, low cost and wide availability, the specificity of both techniques is rather low compared to nuclear medicine techniques. Nuclear medicine techniques, on the other hand, have improved specificity when introduced as a hybrid imaging modality, as they can combine physiological and anatomical information. Two main radiopharmaceuticals are used in nuclear medicine: [99mTc]-methyl diphosphonate ([99mTc]Tc-MDP) from the generator and [18F]sodium fluoride ([18F]NaF) from the cyclotron. The former is used in SPECT imaging, while the latter is used in PET imaging. However, recent studies show that the role of radiolabeled bisphosphonates with gallium-68 (68Ga) and fluorine-18 (18F) may have a potential role in the future. This review, therefore, presents and discusses the brief method for producing current and future potential radiopharmaceuticals for bone metastases.
Bisphosphonates are therapeutic agents that have been used for almost five decades in the treatment of various bone diseases, such as osteoporosis, Paget disease and prevention of osseous complications in cancer patients. In nuclear medicine, simple bisphosphonates such as 99mTc-radiolabelled oxidronate and medronate remain first-line bone scintigraphic imaging agents for both oncology and non-oncology indications. In line with the growing interest in theranostic molecules, bifunctional bisphosphonates bearing a chelating moiety capable of complexing a variety of radiometals were designed. Among them, DOTA-conjugated zoledronate (DOTAZOL) emerged as an ideal derivative for both PET imaging (when radiolabeled with 68Ga) and management of bone metastases from various types of cancer (when radiolabeled with 177Lu). In this context, this report provides an overview of the main medicinal chemistry aspects concerning bisphosphonates, discussing their roles in molecular oncology imaging and targeted radionuclide therapy with a particular focus on bifunctional bisphosphonates. Particular attention is also paid to the development of DOTAZOL, with emphasis on the radiochemistry and quality control aspects of its preparation, before outlining the preclinical and clinical data obtained so far with this radiopharmaceutical candidate.
The production of [18F]Fluorodeoxyglucose ([18F]FDG) using a GE FASTLab2 synthesizer enables to obtain higher radiochemical yields including more robust synthesis process. This work evaluates the performance of GE FASTlab2 and discusses further the regulatory aspects of upgrading a synthesizer. The analytical results after end of synthesis (EOS) demonstrate the superiority of the GE FASTlab2 (71.3% ± 6.7) versus GE Tracerlab MX FDG (57.7% ± 4.2). The FDG Duo performance showed high radiochemical yields after EOS with 72.5% ± 1.5 and 72.9% ± 2.0 for the first and second run. The radiochemical purity for the GE FASTlab2 synthesizer amounted to 99.78% ± 0.1. No radiolabeled intermediate compound (FTAG) was present in the final product solution. These good results were obtained by different FASTlab2 cassette modifications and the synthesis steps involved. Thus a higher amount of precursor, an improved FTAG trapping method, the use of tC18 long plus cartridge, novel FASTlab2 cassette valve design, and nitrogen gas flushing of final tubing was applied. Additionally, this work deals with regulatory aspects which had to be fulfilled during the upgrading process.
Bone metastases are serious complication in the progression of various types of cancer. It determines the requirement of modern nuclear diagnostic tools, including positron emission tomography (PET). In this study the biodistribution of EDTMP labeled with gallium-68 ( ⁶⁸ Ga-EDTMP) prepared at different temperature (20, 50, and 95 °C) was investigated. All experimental studies were performed in healthy intact Wistar rats by measuring the radioactivity in organs and tissues with gamma counter. All ⁶⁸ Ga-EDTMP formulations accumulated predominantly in bones. Only in tibia the uptake of ⁶⁸ Ga-EDTMP prepared at 95 °C was higher (p < 0.05) than ⁶⁸ Ga-EDTMP prepared at 20 °C, but in other bones there weren’t any statistical differences in uptake of ⁶⁸ Ga-EDTMP formulations. The amounts of ⁶⁸ Ga-EDTMP formulations in soft organs and tissues were lower when compared with bones. In conclusion, a temperature of reaction mixture had an influence on the biodistribution of ⁶⁸ Ga-EDTMP in bones.
