53 research outputs found
Production, quality control, biodistribution assessment and preliminary dose evaluation of [177Lu]-tetra phenyl porphyrin complex as a possible therapeutic agent
;Devido às propriedades interessantes do ;177;Lu e da avidez tumoral das tetrafenil porfirinas (TPP), desenvolveu-se a ;177;Lu-tetrafenil porfirina como composto terapêutico potencial. ;177;Lu de atividade específica de 2,6-3 GBq/mg foi obtido por irradiação de amostra de Lu;2;O;3; com fluxo térmico de nêutrons de 4 × 10;13; n.cm;-2;.s;-1;. Sintetizou-se a tetrafenil porfirina e marcou-se com ;177;Lu. A pureza radioquímica do complexo foi estudada usando método de Cromatografia Instantânea de Camada Delgada ( ITLC). A estabilidade do complexo foi checada na formulação final e no ser humano por 48 h. A biodistribuição do composto marcado em órgãos vitais de ratos do tipo selvagem foi estudada por mais de 7 dias. A dose absorvida para cada órgão humano foi calculada pelo método da Dose Médica de Radiação Interna (MIRD). Estudo farmacocinético comparativo detalhado foi efetuado para o cátion ;177;Lu e para o [;177;Lu]-TPP. O complexo foi preparado com pureza radioquímica >;97±1% e atividade específica de 970-1000 MBq/mmol. Os dados de biodistribuição e os resultados dosimétricos mostraram que todos os tecidos receberam uma dose absorvida aproximadamente insignificante devido à rápida excreção do complexo pelo trato urinário. O [;177;Lu]-TPP pode ser um agente interessante de direcionamento do tumor devido à baixa captação pelo fígado e pela dose bem baixa absorvida, de, aproximadamente, 0,036 do corpo humano total.;Due to interesting therapeutic properties of ;177;Lu and tumor avidity of tetraphenyl porphyrins (TPPs), ;177;Lu-tetraphenyl porphyrin was developed as a possible therapeutic compound. ;177;Lu of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu;2;O;3;sample with thermal neutron flux of 4 × 10;13; n.cm;-2;.s;-1;. Tetraphenyl porphyrin was synthetized and labeled with ;177;Lu. Radiochemical purity of the complex was studied using Instant thin layer chromatography (ITLC) method. Stability of the complex was checked in final formulation and human serum for 48 h. The biodistribution of the labeled compound in vital organs of wild-type rats was studied up to 7 d. The absorbed dose of each human organ was calculated by medical internal radiation dose (MIRD) method. A detailed comparative pharmacokinetic study was performed for ;177;Lu cation and [;177;Lu]-TPP. The complex was prepared with a radiochemical purity: >;97±1% and specific activity: 970-1000 MBq/mmol. Biodistribution data and dosimetric results showed that all tissues receive approximately an insignificant absorbed dose due to rapid excretion of the complex through the urinary tract. [;177;Lu]-TPP can be an interesting tumor targeting agent due to low liver uptake and very low absorbed dose of approximately 0.036 to the total body of human
Evaluation of [67Ga]-insulin for insulin receptor imaging
BACKGROUND: Radiolabelled human recombinant insulin can
be used for the imaging of insulin receptors in some tumours
where FDG has natural uptake and diminishes the value of its
imaging.
MATERIAL AND METHODS: Insulin was successively labelled
with [67 Ga]-gallium chloride after conjugation with freshly prepared
cyclic DTPA-dianhydride (HPLC radiochemical purity
assay > 96%) followed by biodistribution studies in normal rats,
white blood cell labelling and preliminary SPECT studies.
RESULTS: In vitro studies demonstrated the retention of radiolabelled
insulin receptor affinity using freshly prepared human
white blood cells at different blood sugar conditions.
Preliminary in vivo studies in a normal rat model was performed
to determine the biodistribution of the radioimmunoconjugate
at up to 44 h. SPECT images revealed high uptake
of the liver.
CONCLUSION: Radiolabelled insulin is stable enough to be
used in biological studies in order to image insulin receptors in
diabetic conditions as well as possible tumour imaging applications.
The data was consistent with other radiolabelled insulin
studies
Production, Quality Control and Pharmacokinetic Studies of 166Ho-EDTMP for Therapeutic Applications
166Ho-EDTMP is a major therapeutic agent which is widely used in bone palliation therapy. In this study, a 166Ho-EDTMP complex was prepared successfully using an in-house synthesized EDTMP ligand and 166HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 1013 ncm−2s−1) of natural Ho(NO3)3 samples (specific activity = 3–5 GBq/mg), dissolved in acidic media. The radiochemical purity of 166Ho-EDTMP was checked by ITLC (>99%) and stability studies in presence of human serum and final preparation were performed. The biodistribution of 166Ho-EDTMP and 166HoCl3 in wild-type rats was checked by scarification. SPECT imaging of 166Ho-EDTMP was also performed in wild-type rats. A comparative accumulation study for 166Ho-EDTMP and 166HoCl3 was performed for vital organs up to 48h. Significant bone accumulation (>70%) of the tracer in 48h was observed
Grafting of a novel gold(III) complex on nanoporous MCM-41 and evaluation of its toxicity in Saccharomyces cerevisiae
The goal of this research was to investigate the potential of newly synthesized gold complex trichloro(2,4,6-trimethylpyridine)Au(III) as an anticancer agent. The gold(III) complex was synthesized and grafted on nanoporous silica, MCM-41, to produce AuCl3@PF-MCM- 41 (AuCl3 grafted on pyridine-functionalized MCM-41). The toxicity of trichloro(2,4,6- trimethylpyridine)Au(III) and AuCl3@PF-MCM-41 in Saccharomyces cerevisiae (as a model system) was studied. The gold(III) complex showed a mid cytotoxic effect on yeast viability. Using the drug delivery system, nanoporous MCM-41, the gold(III) complex became a strong inhibitor for growth of yeast cells at a very low concentration. Furthermore, the animal tests revealed a high uptake of AuCl3@PF-MCM-41 in tumor cells. The stability of the compound was confirmed in human serum
Optimized Production Assessment, Compartmental Modeling and Dosimetric Evaluation of 177Lu- PSMA-617 for Clinical Trials
177Lu-PSMA-617 was prepared at the optimized conditions (95°C, 15-18 µg peptide, 35-40 min; solid phase purification) using 177Lu obtained from 176Lu(n, γ)177Lu reaction(>98%, ITLC, HPLC, S.A. 22-24 TBq/mM) followed by stability (up to 48 h), biodistribution studies (up to 168 h), planar imaging, compartmental modeling and dosimetry estimations via Sparks’s extrapolation method in human organs. Kidney is the critical organ with the dose of 0.067 mGy/MBq and the radiopharmaceutical can be safely used in trials considering the human dose
Preparation and quality control of 177 Lu-chitosan for radiosynovectomy
ABSTRACT Introduction: Rheumatoid arthritis (RA) is the most common autoimmune disease, leading to the destruction of the joints and causing pain, disability, and immobility in the patients. Radiosynovectomy (RSV) has been applied as an effective treatment for the patients with resistant synovitis after failure of long-term pharmacotherapy and intra-articular steroid injection for more than 50 years. Several radiopharmaceuticals have been developed for RSV so far, but still development of new radiophamaceuticals is of crucial interest. In this research, the 177 Lu-chitosan complex ( 177 Lu-CHITO) was introduced as a new agent for RSV. Methods: 177 Lu was produced by irradiation of a natural Lu 2 O 3 target at a thermal neutron flux of approximately 4 × 1
Morbidity and mortality from road injuries: results from the Global Burden of Disease Study 2017
BackgroundThe global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years.MethodsWe used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury.ResultsGlobally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change.ConclusionsWhile road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented
Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study
Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future
Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017
Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe
Estimating global injuries morbidity and mortality : methods and data used in the Global Burden of Disease 2017 study
Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.Peer reviewe
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