RESUMO
PURPOSES: Size exclusion chromatography (SEC) is widely used to characterize molecular size variants of antibody drugs. However, SEC analysis is hindered by secondary interactions (or nonspecific interactions) between proteins and stationary phase packing, which result in poor column efficiency. Previous studies have reported that chaotropic salt can inhibit these interactions, but the corresponding applications of this aspect are relatively rare. Therefore, this study introduces a novel approach using sodium iodide (NaI) as a mobile-phase component in SEC and investigates the influence of the mobile-phase composition on secondary interactions. METHODS: SEC analysis was performed on one antibody-drug conjugate and four monoclonal antibodies (mAbs) using three different mobile-phase systems (i.e., sodium chloride/L-arginine hydrochloride/NaI mobile phases system) to compare the column efficiency. Subsequently, mAb-1 was used as a model to investigate the effects of these factors on secondary interactions by adjusting the ionic strength (salt concentration) and pH of the NaI mobile-phase system. RESULTS: NaI exhibits superior column efficiency performance in the SEC analysis of most products. The ionic strength will affect nonideal electrostatic and hydrophobic interaction. An appropriate ionic strength can inhibit electrostatic interactions, while an excessive ionic strength increases hydrophobic interactions. pH primarily influences electrostatic interactions. Determining the appropriate pH necessitates consideration of the isoelectric point of the protein and the pH tolerance of the column. CONCLUSIONS: In SEC analysis, using NaI as the salt component in the mobile phase reduces secondary interactions and improves column efficiency. This approach is advantageous for samples with intense secondary interactions and is a suitable alternative.
Assuntos
Anticorpos Monoclonais , Cromatografia em Gel , Imunoconjugados , Iodeto de Sódio , Anticorpos Monoclonais/química , Cromatografia em Gel/métodos , Imunoconjugados/química , Iodeto de Sódio/química , Concentração Osmolar , Interações Hidrofóbicas e Hidrofílicas , Concentração de Íons de Hidrogênio , Cloreto de Sódio/química , Eletricidade Estática , Arginina/químicaRESUMO
The integration of the ORION digital signal processing-based MCA system coupled with a 3â³ × 3â³ NaI(Tl) detector assembly with a GM detector for counting beta (ß) has eliminated the need for a standalone ß-γ method in which U3O8 is determined by gross ß and gross γ counting. Uraniferous and mixed U-Th samples were taken up for study and compared with the results obtained from Canberra p-type coaxial high resolution gamma ray spectrometry detector. In uraniferous samples, U3O8 values obtained are within ±10%, whereas in the case of mixed U-Th samples, U3O8 values are within ±15%. Regression graphs drawn between the outcomes from the two analytical systems indicate R2 > 0.95 for Ra(eU3O8) and ThO2. In uraniferous samples, the R2 value for U3O8 was found to be > 0.99, but in mixed U-Th samples, it is 0.92. The closeness of agreement between the results obtained from two methods at various concentrations over the analytical range shows that the integrated system is suitable for the quantitative determination of eU3O8, U3O8, Ra(eU3O8), ThO2 and K in geological rock samples.
Assuntos
Monitoramento de Radiação , Espectrometria gama , Monitoramento de Radiação/métodos , Monitoramento de Radiação/instrumentação , Espectrometria gama/métodos , Espectrometria gama/instrumentação , Partículas beta , Urânio/análise , Európio/química , Európio/análise , Dosimetria Termoluminescente/instrumentação , Dosimetria Termoluminescente/métodos , Processamento de Sinais Assistido por Computador , Tálio/análise , Tório/análise , Iodeto de SódioRESUMO
The goal of this study was to apply the principles of analytical quality by design (AQbD) to the analytical method for determining the radiochemical purity (PQR) of the radiopharmaceutical sodium iodide 131I oral solution, utilizing thin-layer chromatography (TLC) with a radio-TLC scanner, which also enables the evaluation of product quality. For AQbD, the analytical target profile (ATP), critical quality attributes (CQA), risk management, and the method operable design region (MODR) were defined through response surface methodology to optimize the method using MINITAB® 19 software. This study encompassed the establishment of a control strategy and the validation of the method, including the assessment of selectivity, linearity, precision, robustness, detection limit, quantification limit, range, and the stability of the sample solution. Under the experimental conditions, the method parameters of the TLC scanner were experimentally demonstrated and optimized with an injection volume of 3 µL, a radioactive concentration of 10 mCi/mL, and a carrier volume of 40 µL. Statistical analysis confirmed the method's selectivity for the 131I iodide band Rf of 0.8, a radiochemical impurity IO3- Rf of 0.6, a linearity from 6.0 to 22.0 mCi/mL, and an intermediate precision with a global relative standard deviation (RSD) of 0.624%. The method also exhibited robustness, with a global RSD of 0.101%, a detection limit of 0.09 mCi/mL, and a quantification limit of 0.53 Ci/mL, meeting the prescribed range and displaying stability over time (at 0, 2, and 20 h) with a global RSD of 0.362%, resulting in consistent outcomes. The development of a method based on AQbD facilitated the creation of a design space and an operational space, with comprehensive knowledge of the method's characteristics and limitations. Additionally, throughout all operations, compliance with the acceptance criteria was verified. The method's validity was confirmed under the established conditions, making it suitable for use in the manufacturing process of sodium iodide 131I and application in nuclear medicine services.
Assuntos
Radioisótopos do Iodo , Compostos Radiofarmacêuticos , Iodeto de Sódio , Cromatografia em Camada Fina/métodos , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/análise , Radioisótopos do Iodo/análise , Iodeto de Sódio/química , Administração Oral , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Gamma camera imaging, including single photon emission computed tomography (SPECT), is crucial for research, diagnostics, and radionuclide therapy. Gamma cameras are predominantly based on arrays of photon multipliers tubes (PMTs) that read out NaI(Tl) scintillation crystals. In this way, standard gamma cameras can localize É£-rays with energies typically ranging from 30 to 360 keV. In the last decade, there has been an increasing interest towards gamma imaging outside this conventional clinical energy range, for example, for theragnostic applications and preclinical multi-isotope positron emission tomography (PET) and PET-SPECT. However, standard gamma cameras are typically equipped with 9.5 mm thick NaI(Tl) crystals which can result in limited sensitivity for these higher energies. PURPOSE: Here we investigate to what extent thicker scintillators can improve the photopeak sensitivity for higher energy isotopes while attempting to maintain spatial resolution. METHODS: Using Monte Carlo simulations, we analyzed multiple PMT-based configurations of gamma detectors with monolithic NaI (Tl) crystals of 20 and 40 mm thickness. Optimized light guide thickness together with 2-inch round, 3-inch round, 60 × 60 mm2 square, and 76 × 76 mm2 square PMTs were tested. For each setup, we assessed photopeak sensitivity, energy resolution, spatial, and depth-of-interaction (DoI) resolution for conventional (140 keV) and high (511 keV) energy É£ using a maximum-likelihood algorithm. These metrics were compared to those of a "standard" 9.5 mm-thick crystal detector with 3-inch round PMTs. RESULTS: Estimated photopeak sensitivities for 511 keV were 27% and 53% for 20 and 40 mm thick scintillators, which is respectively, 2.2 and 4.4 times higher than for 9.5 mm thickness. In most cases, energy resolution benefits from using square PMTs instead of round ones, regardless of their size. Lateral and DoI spatial resolution are best for smaller PMTs (2-inch round and 60 × 60 mm2 square) which outperform the more cost-effective larger PMT setups (3-inch round and 76 × 76 mm2 square), while PMT layout and shape have negligible (< 10%) effect on resolution. Best spatial resolution was obtained with 60 × 60 mm2 PMTs; for 140 keV, lateral resolution was 3.5 mm irrespective of scintillator thickness, improving to 2.8 and 2.9 mm for 511 keV with 20 and 40 mm thick crystals, respectively. Using the 3-inch round PMTs, lateral resolutions of 4.5 and 3.9 mm for 140 keV and of 3.5 and 3.7 mm for 511 keV were obtained with 20 and 40 mm thick crystals respectively, indicating a moderate performance degradation compared to the 3.5 and 2.9 mm resolution obtained by the standard detector for 140 and 511 keV. Additionally, DoI resolution for 511 keV was 7.0 and 5.6 mm with 20 and 40 mm crystals using 60 × 60 mm2 square PMTs, while with 3-inch round PMTs 12.1 and 5.9 mm were obtained. CONCLUSION: Depending on PMT size and shape, the use of thicker scintillator crystals can substantially improve detector sensitivity at high gamma energies, while spatial resolution is slightly improved or mildly degraded compared to standard crystals.
Assuntos
Câmaras gama , Método de Monte Carlo , Iodeto de Sódio , Iodeto de Sódio/química , Luz , Contagem de Cintilação/instrumentação , FótonsRESUMO
Radioactive iodine therapy (RIT) is an effective, safe, and cheap method in benign and malignant thyroid diseases. There is still an unresolved question of whether RIT treatment also plays a role in the treatment of, for example, breast cancer, lung cancer, or glioblastoma multiforme (GBM). These studies are currently being carried out in rats in combination with genes, but it may be an interesting challenge to assess "pure" RIT alone, thanks to the expression of sodium iodide symporter (NIS), is effective in other organ nodules, both benign and malignant. Cloning of the NIS in 1996 provided an opportunity to use NIS as a powerful theranostic transgene. In addition, NIS is a sensitive reporter gene that can be monitored by high-resolution PET imaging using the radiolabels [¹²4I]sodium iodide ([¹²4I]NaI) or [18F] tetrafluoroborate ([¹8F]TFB). Based on published positron emission tomography (PET) results, [¹²4I]sodium iodide and internally synthesized [18F]TFB were compared in an orthotopic animal model of NIS-expressing glioblastoma. The results showed improved image quality using [¹8F]TFB. Based on these results, we will be able to extend the NIS gene therapy approach using non-viral gene delivery vehicles to target orthotopic tumour models with low-volume disease such as GBM. Is it possible to treat RIT alone without using the NIS gene in GBM? After all, the NIS symporter was detected not only in the thyroid gland, but also in different tumours. The administration of RIT is completely harmless; the only complication is hypothyroidism. Indeed, recently it has been shown that, for example, in the case of thyroid cancer, the maximum RIT is 37000 MBq (1000 mCi). When beneficial effects of therapy in GBM are not possible (e.g. neurosurgery, modulated electro-hyperthermia, chemotherapy, immunotherapy, cancer vaccines, or oncolytic viruses), could RIT provide a "revolution" using NIS?
Assuntos
Glioblastoma , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Ratos , Animais , Neoplasias da Glândula Tireoide/genética , Radioisótopos do Iodo/uso terapêutico , Glioblastoma/diagnóstico por imagem , Glioblastoma/radioterapia , Iodeto de Sódio , Neoplasias Pulmonares/tratamento farmacológico , AntiviraisRESUMO
Iodine is an essential micronutrient for producing thyroid hormone (TH); however, iodide excess can lead to adverse thyroidal effects. Unfortunately, the lack of a proper in vitro model system hampered the studies of the effect of iodide excess on thyroid physiology and pathology. Here, we demonstrated that excessive iodide intake downregulated the genes related to TH synthesis in the thyroids of mice. Since sodium iodide has no effect on these genes in cultured cell lines, we developed a three-dimensional (3D) culture system to enable the murine thyrocytes to form organoids in vitro with thyroid follicle-like structures and function and found that the in vivo effect of iodide excess could be mimicked in these thyroid organoids. Our data indicate that iodide excess mainly activated the XBP1-mediated unfolded protein response in both murine thyroid and thyroid organoids, while activation of XBP1 was able to mimic the sodium iodide effect on genes for the synthesis of TH in murine thyroid organoids. Lastly, our results suggest that XBP1 might transcriptionally repress the genes involved in the synthesis of TH. Based on these findings, we propose that iodide excess inhibits the transcription of genes related to TH synthesis through a mechanism involving XBP1-mediated action.
Assuntos
Iodetos , Iodeto de Sódio , Camundongos , Animais , Iodeto de Sódio/metabolismo , Iodeto de Sódio/farmacologia , Hormônios Tireóideos/metabolismo , Glândula Tireoide/metabolismo , Linhagem Celular , Proteína 1 de Ligação a X-Box/metabolismoRESUMO
ABSTRACT: The performance of several gamma detectors was investigated for emergency urine bioassay screening of two radionuclides of concern: 131 I and 137 Cs. Unspiked artificial urine samples were measured for 10 min each on four different gamma detectors: 80% relative efficiency high-purity Ge detector in standard shielding, 102% low-background high-purity Ge detector equipped with top muon shield, 78% high-purity Ge well detector in standard shielding, and 4â³ × 4â³ NaI well detector in standard shielding. The measured gamma spectra were analyzed in two ways: (1) for the 364-keV peak region of 131 I and 662-keV peak region of 137 Cs and (2) for the total counts in the full energy spectrum (50-2,048 keV). The results were analyzed using the principles of signal detection theory according to the Currie's formalism extended by a complete uncertainty propagation. This enabled calculation of the detection capability in terms of detection limit (Bq L -1 ) of urine, the latter referred to as minimum detectable activity. The NaI well detector had the lowest minimum detectable activities for total spectra, whereas the high-purity Ge well detector had the lowest peak minimum detectable activity values. Minimum detectable inhalation and ingestion intakes from urine bioassay were calculated from the minimum detectable activity values for urine collection 1 d, 1 wk, and 1 mo past the initial intake. The calculated intakes were compared with annual limits on intake. The results are interpreted with respect to a large-scale radiological emergency response.
Assuntos
Germânio , Radioatividade , Humanos , Iodetos , Iodeto de Sódio , Limite de Detecção , Radioisótopos de Césio , Radioisótopos do Iodo , SódioRESUMO
Nowadays, the use of radioactive materials has increased due to recent progress in nuclear technology, but concerns about the missing or smuggling of radioactive materials have persisted. Nuclear threats such as terrorist attacks or the malicious use of radioactive materials out of regulatory control (MORC) are always severe problems that can result in adverse environmental, health, economic, and security effects. Applying new technologies to monitor and track MORC will prevent radioactive materials from being illegally transported across borders or from one place to another. In this research, we have constructed a detection system to automatically and remotely localize multiple mobile gamma-emitting radiation sources among other objects by combining an IP camera and a sodium iodide detector. An algorithm for the detection system has been developed to identify the objects' paths from camera data and correlate radiation data with the paths to detect contaminated objects. We evaluated the system using two weak radioactive sources (Co-60, Cs-137), which were hidden on moving objects, and succeeded in finding harmful targets. The results have also shown that by increasing the number of contaminated sources from one to two, the detection accuracy decreases by about 2.5 times. However, by doubling the speed of mobile targets, the detection accuracy improved by about 30%. Detecting and tracking MORC with a single detection system is limited to small regions. By equipping many surveillance cameras in a city with relatively inexpensive radioactive detectors, a network sensing system is established to find radioactive hotspots in a smart city.
Assuntos
Radioisótopos de Césio , Iodeto de Sódio , AlgoritmosRESUMO
In this research, we propose a novel nonlinear delta-function photonic crystal for detecting sodium iodide (NaI) solution of different concentrations. The suggested structure comprises 50 delta stacks of GaP in an aqueous solution of NaI. These stacks are considered to have weak defocusing nonlinearity in the order of 10-6 (V/m)-2. Due to nonlinearity of the design, a defect-like resonance is formed within the photonic band gap. Thus, the detection of NaI with different concentrations can be easily investigated without the inclusion of a defect through the photonic crystal structure. The effects of both the linear part of the refractive index of GaP layers and nonlinear coefficient on the transmittance value are thoroughly discussed. The numerical findings investigate that the resonant peak begins to split at some critical nonlinearity. In our proposed structure, splitting occurs at about - 12 × 10-6 (V/m)-2. In this regard, the suggested sensor provides a high sensitivity of 409.7 nm/RIU and a wonderful detection limit of 0.0008.
Assuntos
Técnicas Biossensoriais , Iodeto de Sódio , Óptica e Fotônica , Refratometria , FótonsRESUMO
Since the first introduction of sodium iodide I-131 for use with thyroid patients almost 80 years ago, more than 50 radiopharmaceuticals have reached the markets for a wide range of diseases, especially cancers. The nuclear medicine paradigm also shifts from solely molecular imaging or radionuclide therapy to imaging-guided radionuclide therapy, which is deemed a vital component of precision cancer therapy and an emerging medical modality for personalized medicine. The imaging-guided radionuclide therapy highlights the systematic integration of targeted nuclear diagnostics and radionuclide therapeutics. Regarding this, nuclear imaging serves to "visualize" the lesions and guide the therapeutic strategy, followed by administration of a precise patient specific dose of radiotherapeutics for treatment according to the absorbed dose to different organs and tumors calculated by dosimetry tools, and finally repeated imaging to predict the prognosis. This strategy leads to significantly enhanced therapeutic efficacy, improved patient outcomes, and manageable adverse events. In this review, we provide an overview of imaging-guided targeted radionuclide therapy for different tumors such as advanced prostate cancer and neuroendocrine tumors, with a focus on development of new radioligands and their preclinical and clinical results, and further discuss about challenges and future perspectives.
Assuntos
Neoplasias , Compostos Radiofarmacêuticos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Imagem Molecular , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Iodeto de SódioRESUMO
The environmental radiation exposure in Canada has been monitored since 2002 by Health Canada's Fixed Point Surveillance network. The network consists of over eighty 7.6 cm × 7.6 cm sodium iodide spectrometers, and routinely reports to the public the environmental gamma radiation level throughout Canada. This paper describes the latest dose calibrations to air kerma and ambient dose equivalent for the future upgraded network. The calibration curves were developed using Monte Carlo techniques and further optimized via experiments in various reference fields. The dose calibration was validated over a wide range of gamma energy, dose measurement range, and angle of incidence under laboratory conditions. In environmental monitoring situations, the angular distribution of radiation exposure was analytically calculated by assuming a semi-infinite plume source, semi-infinite planar source, and infinite volume sources for the respective exposure scenarios of radioactive plume, ground contamination, and soil source. By coupling the resultant radiation angular distribution with detector's angular variation on dose response, the overall accuracy of dose measurement in each of these environmental scenarios was estimated. The accuracy is expected to be within ±3.7% for plume radiation, -5.6% for 137Cs ground contamination, and 0% to -17.1% for soil radioactive sources. The under-estimation for soil sources is mainly caused by absorption of radiation in the electronic system underneath the crystal.
Assuntos
Monitoramento de Radiação , Calibragem , Método de Monte Carlo , Doses de Radiação , Monitoramento de Radiação/métodos , Iodeto de Sódio , SoloRESUMO
Tissue necrosis is a serious but rare complication of sclerotherapy. Early detection and targeted management are essential to prevent progression and minimise serious complications. In the first instalment of this paper, we reviewed the pathogenic mechanisms of post-sclerotherapy necrosis. Here, we describe risk minimisation and management strategies.Risk factors must be addressed to reduce the chance of necrosis following sclerotherapy. These may be treatment-related including poor choice of sclerosant type, concentration, volume or format, poor injection technique, suboptimal ultrasound visualisation and treatment of vessels in high-risk anatomical areas. Risk factors specific to individual patients should be identified and optimised pre-operatively.Tissue necrosis is more likely to occur with extravasation of irritant sclerosants such as absolute alcohol, sodium iodide, bleomycin and hypertonic saline, whereas extravasation of foam detergent sclerosants rarely results in tissue loss. Proposed treatments for extravasation of irritant sclerosants include infiltration of an isotonic fluid and hyaluronidase. Management of inadvertent intra-arterial injections may require admission for neurovascular observation and monitoring for ischaemia, intravenous systemic steroids, anticoagulation, thrombolysis and prostanoids infusion when required. Treatment of veno-arteriolar reflex vasospasm (VAR-VAS) necrosis follows the same protocol involving systemic steroids but rarely requires hospital admission and may not require anticoagulation.In general, treatment of post-sclerotherapy necrosis is challenging and most proposed treatment measures are not evidence-based and only supported by anecdotal personal experience of clinicians. Despite all measures, once the necrosis has set in, it is very difficult to reverse the process and all measures described here may only be useful in prevention of progression and extension of the ulceration.Mid to long-term measures include addressing exacerbating factors, management of medical and psychosocial comorbidities, treatment of secondary infections and referrals to relevant specialists. All ulcers should be managed with compression and prescribed dressing regimes in line with the healing stage of the ulcer.
Assuntos
Soluções Esclerosantes , Escleroterapia , Anticoagulantes , Bleomicina , Detergentes , Etanol , Humanos , Hialuronoglucosaminidase , Irritantes , Necrose/induzido quimicamente , Necrose/tratamento farmacológico , Prostaglandinas , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Iodeto de SódioRESUMO
The purpose of this study was to identify a method to accurately separate small microplastics (<100 µm) from soil and sediment. We initially conducted spike-and-recovery tests using polyethylene microbeads and density separation and found that the recovery rate of microplastic particles smaller than 100 µm was less than 60%. This result suggested that previous reports have underestimated the concentrations of microplastics smaller than 100 µm in soil. When polyvinyl pyrrolidone was added and dispersed in a heavy liquid, the recovery rate exceeded 90%, regardless of the microplastic particle size. This improved recovery rate was independent of the type of polymer (polyethylene, polypropylene, polystyrene, polyethylene terephthalate, or nylon 6) and the physicochemical properties of the soil (Andisols, Entisols, or Ultisols), and the method was also effective for marine and lake sediments. Using this method, we measured microplastic concentrations in paddy soil. The results showed that the most common particle size, 20-100 µm, accounted for 64% of all microplastics. Accurate separation from the soil of fractions smaller than 100 µm, which account for the majority of microplastics in soil, will enable an accurate assessment of the impact of microplastics on the soil ecosystem. The method identified in this study can serve as the basic technique for achieving that goal.
Assuntos
Microplásticos , Poluentes Químicos da Água , Ecossistema , Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Plásticos , Polietileno , Polietilenotereftalatos , Polímeros , Polipropilenos , Poliestirenos , Polivinil , Povidona , Iodeto de Sódio , Solo , Poluentes Químicos da Água/análiseRESUMO
Therapeutic iodoform (CHI3) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation.
Assuntos
Materiais Restauradores do Canal Radicular , Hidróxido de Cálcio , Materiais Restauradores do Canal Radicular/farmacologia , Iodeto de Sódio , Dente Decíduo , ÁguaRESUMO
ABSTRACT: Intake of 131I by nuclear medicine technologists and physician Authorized Users was evaluated using bioassay data from administration of 131I sodium iodide in capsular form during a 5-year period. Maximum estimated annual intake of 131I sodium iodide, based on bioassay measurements performed at 24 hours post administration, ranged from 10.9 to 35.6 kBq for all staff. Intake by Authorized Users was higher than that by nuclear medicine technologists due to state requirement for Authorized Users to physically administer therapeutic dosages of radiopharmaceuticals. All intake values were less than 10% of the 131I thyroid ALI of 50 microcurie3 (1,850 kBq), indicating that monitoring may be discontinued for staff participating in routine administration of 131I capsules in which volatilization is not suspected. Elimination of bioassay performance has permitted more flexibility in patient scheduling and improved workflow and efficiency.
Assuntos
Radioisótopos do Iodo , Iodeto de Sódio , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Iodeto de Sódio/uso terapêutico , Glândula TireoideRESUMO
By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl-NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis-oxathiolane products with up to 95% yield and >20:1 dr. This telescoped sequence is followed by recrystallization and borohydride reduction, resulting in rapid synthesis of (±)-FTC/3TC from a tartrate diester.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/farmacologia , Desoxicitidina/uso terapêutico , Emtricitabina/uso terapêutico , Glicosilação , Infecções por HIV/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Iodeto de Sódio/uso terapêutico , Compostos de Trimetilsilil , ÁguaRESUMO
Preoperative localization of pathologic parathyroids is crucial for minimally invasive treatment of primary hyperparathyroidism (PHPT). This study compared contrast-enhanced 18F-fluorocholine PET/CT, cervical ultrasonography (CU), and conventional scintigraphic imaging modalities (MIBI scintigraphy, consisting of 99mTc-sestamibi/123I-sodium iodide SPECT/CT, 99mTc-sestamibi/123I-sodium iodide planar subtraction imaging, and 99mTc-sestamibi planar dual-phase imaging), combined and individually, for preoperative localization of hyperfunctional parathyroids in PHPT. The gold standard was histologic examination. Methods: Data from consecutive patients with clinically suspected PHPT were retrospectively collected. All 3 imaging modalities were systematically performed. The ability of 18F-fluorocholine PET/CT, CU, and MIBI scintigraphy to identify a hyperfunctional parathyroid and specify the side or identify an ectopic location was noted. Patients underwent surgical exploration if at least 1 examination was positive. The findings of CU + MIBI scintigraphy combined were considered positive if CU and MIBI scintigraphy separately showed a hyperfunctional parathyroid gland on the same side or in the same ectopic location; any findings other than these were considered negative. The composite judgment criterion for pathologic parathyroid was a combination of histologic analysis and normalization of parathyroid hormone and calcium levels. Results: In total, 149 pathologic parathyroids were found in 143 of the 144 included patients. 18F-fluorocholine PET/CT diagnosed 148 of 149 pathologic parathyroids. Only 4 false-positives and 1 false-negative were found. The 18F-fluorocholine PET/CT sensitivity of 99.3% was superior to that of CU, at 75.2% (P < 0.0001); MIBI scintigraphy, at 65.1% (P < 0.0001); and CU + MIBI scintigraphy, at 89.9%, (P = 0.0009). Five of the 5 ectopic locations were diagnosed by 18F-fluorocholine PET/CT, 2 of the 5 by MIBI scintigraphy, and none by CU. Accuracy was better for 18F-fluorocholine PET/CT, at 98%, than for CU, at 84% (P < 0.0001); MIBI scintigraphy, at 81% (P < 0.0001); or CU + MIBI scintigraphy, at 91% (P < 0.0001). Among the 72 (50%) patients who had a negative CU + MIBI scintigraphy result, 18F-fluorocholine PET/CT correctly identified hyperfunctional thyroids in 70 (97.2%). Average uptake in the 18F-fluorocholine PET/CT hyperfunctional parathyroid was higher than that in the adjacent thyroid (SUVmax adjusted for lean body mass, 6.45 vs. 2.15) (P < 0.0001). Conclusion: The accuracy of 18F-fluorocholine PET/CT is higher than that of CU and MIBI scintigraphy for localization of hyperfunctional parathyroids, justifying the systematic use of 18F-fluorocholine PET/CT as the first-line method for PHPT diagnosis.
Assuntos
Hiperparatireoidismo Primário , Humanos , Colina/análogos & derivados , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/patologia , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Cintilografia , Estudos Retrospectivos , Iodeto de Sódio , Tecnécio Tc 99m Sestamibi , Ultrassonografia/métodosRESUMO
A series of novel heteroditopic halogen bonding (XB) receptor functionalised silica based materials, containing mono- and bis-iodotriazole benzo-15-crown-5 groups are investigated for the cooperative binding and extraction of sodium halide ion-pair species from aqueous solution. Characterisation of the XB materials by CHN elemental analysis, 13 C CP/MASâ NMR and ATR-FTIR spectroscopies confirms and quantifies the successful incorporation of the ion-pair receptor frameworks to the silica material. ICP-MS solid-liquid extraction studies demonstrate the bidentate XB functionalised material is capable of NaI extraction from water. Importantly, cooperative XB-mediated sodium halide ion-pair binding is determined to be crucial to the material's extraction capabilities, impressively demonstrating a two-fold enhancement in sodium iodide extraction efficiency relative to a heteroditopic hydrogen bonding receptor functionalised silica material analogue.
Assuntos
Halogênios , Iodeto de Sódio , Ânions , Ligação de Hidrogênio , ÍonsRESUMO
Introducción: La aplicación de actividades fijas en el tratamiento del hipertiroidismo con I131 (yoduro de sodio, conocido también como radioyodo), es el método más usado en nuestro país, a pesar de la individualidad morfo-funcional que caracteriza esta afección. Sin embargo, no existe aún, un consenso internacional sobre la dosis más conveniente para cada caso, y por ende, los resultados no siempre son los deseados. Objetivo: Evaluar la aplicabilidad de varios métodos de cálculo de dosis paciente-específica para el tratamiento de hipertiroidismo con yoduro de sodio. Métodos: Se realizó un análisis de los resultados de varios métodos de cálculo de dosis recomendados internacionalmente a partir de la actividad fija prescrita en 10 pacientes, con el empleo de tecnologías y herramientas ya desarrolladas y disponibles en el país. Se evaluó la variabilidad inter-especialista y su impacto en la dosis planificada para el tratamiento. Resultados: El uso de la información incompleta de la biodistribución y farmacocinética del paciente produjo diferencias entre -42 por ciento y 37 por ciento de las dosis para el mismo paciente. El resultado de la comparación del método de cálculo recomendado por la Sociedad Europea de Medicina Nuclear, manejando la masa por gammagrafía-2D / 3D y por ultrasonido, arrojó diferencias no significativas entre sí. La variabilidad inter-especialista de las actividades prescrita mostró diferencias significativas, que arrojan sobre el mismo paciente, discrepancias entre 44Gy y 243Gy de las dosis terapéuticas a recibir, situación que puede comprometer el éxito del tratamiento y producir efectos secundarios no deseados. Conclusiones: Las técnicas dosimétricas paciente-específicas se pueden implementar satisfactoriamente en nuestro país. Las diferencias numéricas encontradas, especialmente la variabilidad inter-especialista, demuestran la no estandarización terapéutica, lo que apoya el uso de la farmacocinética paciente-específica pre terapéutica y la masa por gammagrafía-3D para planificar el tratamiento siempre que sean posible(AU)
Introduction: Despite of its typical morpho-functional individuality, fixed activities remain as the most used method in Cuba for hyperthyroidism treatment with I (sodium iodide, also known as radioiodine). However, there is not yet an international consensus on the most convenient doses for each case, so, the results are not always the desired ones. Objective: To evaluate the applicability of various patient-specific dose calculation methods for the treatment of hyperthyroidism with sodium iodide. Methods: It was carried out an analysis in 10 patients of the results of some methods for dose calculation from the prescribed fixed activity recommended internationally, with the use of technologies and tools already developed and available in the country. The inter-specialist variability and its impact in the planned dose for the treatment were assessed. Results: The use of uncompleted biodistribution and pharmacokinetics information of the patient showed differences between -42 percent and 37 percent in the doses for the same patient. The outcome of the comparison of the calculation method recommended by the European Society of Nuclear Medicine managing the mass by 3D/2D gammagraphy and ultrasound, presented no significant discrepancies among them. The inter-specialist variability of prescribed activity was statistically significant, and it can produce in the same patient differences between 44Gy and 243Gy of the therapeutic doses, which could affect the treatment success and lead to unnecessary side effects. Conclusions: The patient´s personalized calculation methods can be satisfactorily applied in Cuba. The numeric differences found, especially inter-specialist variability, show the lack of therapeutic standardization, which supports the use of pre-therapeutic patient-specific pharmacokinetics and the mass by 3D-gammagraphy to plan the treatment when possible(AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Iodeto de Sódio/uso terapêutico , Farmacocinética , Hipotireoidismo/terapia , Medicina Nuclear/métodos , Padrões de ReferênciaRESUMO
The PtII linker [ethylenediamineplatinum(II)]2+ , coined Lx, has emerged as a novel non-conventional approach to antibody-drug conjugates (ADCs) and has shown its potential in preclinical inâ vitro and inâ vivo benchmark studies. A crucial improvement of the Lx conjugation reaction from initially <15 % to ca. 75-90 % conjugation efficiency is described, resulting from a systematic screening of all relevant reaction parameters. NaI, a strikingly simple inorganic salt additive, greatly improves the conjugation efficiency as well as the conjugation selectivity simply by exchanging the leaving chloride ligand on Cl-Lx-drug complexes (which are direct precursors for Lx-ADCs) for iodide, thus generating I-Lx-drug complexes as more reactive species. Using this iodide effect, we developed a general and highly practical conjugation procedure that is scalable: our lead Lx-ADC was produced on a 5â g scale with an outstanding conjugation efficiency of 89 %.