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1.
Science ; 384(6702): 1335-1339, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38900872

RESUMO

Vegetation and soils are taking up approximately 30% of anthropogenic carbon dioxide emissions because of small imbalances in large gross carbon exchanges from productivity and turnover that are poorly constrained. We combined a new budget of radiocarbon produced by nuclear bomb testing in the 1960s with model simulations to evaluate carbon cycling in terrestrial vegetation. We found that most state-of-the-art vegetation models used in the Coupled Model Intercomparison Project underestimated the radiocarbon accumulation in vegetation biomass. Our findings, combined with constraints on vegetation carbon stocks and productivity trends, imply that net primary productivity is likely at least 80 petagrams of carbon per year presently, compared with the 43 to 76 petagrams per year predicted by current models. Storage of anthropogenic carbon in terrestrial vegetation is likely more short-lived and vulnerable than previously predicted.


Assuntos
Ciclo do Carbono , Dióxido de Carbono , Carbono , Plantas , Biomassa , Carbono/metabolismo , Carbono/análise , Dióxido de Carbono/metabolismo , Dióxido de Carbono/análise , Radioisótopos de Carbono/análise , Armas Nucleares , Plantas/metabolismo
2.
BMC Cancer ; 24(1): 736, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879476

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. METHODS: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. DISCUSSION: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. TRIAL REGISTRATION: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020-000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020-01, version 3.2, date 18.09.2020.


Assuntos
Neoplasias Encefálicas , Progressão da Doença , Glioblastoma , Metionina , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico , Radioisótopos de Carbono , Glioblastoma/diagnóstico por imagem , Glioblastoma/terapia , Glioblastoma/diagnóstico , Glioblastoma/radioterapia , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Compostos Radiofarmacêuticos/uso terapêutico , Planejamento da Radioterapia Assistida por Computador/métodos
3.
PLoS One ; 19(6): e0302645, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38924012

RESUMO

The Kyrenia Ship, found off the north coast of Cyprus, is a key vessel in the history of scientific underwater excavations and in the history of Greek shipbuilding. The first volume of the site's final publication appeared in 2023 and provides detailed archaeological information tightly constraining the dating of the ship. A very specific date range is proposed: ca. 294-290 BCE, but is based on a less than certain reading of one coin recovered from the ship. While there is clear benefit to finding high-precision dates for the Kyrenia Ship and its rich assemblage using independent scientific dating (combined with Bayesian chronological modeling), efforts to do so proved more challenging and complex than initially anticipated. Strikingly, extensive radiocarbon dating on both wooden materials from the ship and on short-lived contents from the final use of the ship fail to offer dates using the IntCal20 calibration curve-the current Northern Hemisphere radiocarbon calibration curve at the time of writing-that correspond with the archaeological constraints. The issue rests with a segment of IntCal20 ca. 350-250 BCE reliant on legacy pre-AMS radiocarbon data. We therefore measured new known-age tree-ring samples 350-250 BCE, and, integrating another series of new known-age tree-ring data, we obtained a redefined and more accurate calibration record for the period 433-250 BCE. These new data permit a satisfactory dating solution for the ship and may even indicate a date that is a (very) few years more recent than current estimations. These new data in addition confirm and only very slightly modify the dating recently published for the Mazotos ship, another Greek merchant ship from the southern coast of Cyprus. Our work further investigated whether ship wood samples impregnated with a common preservative, polyethylene glycol (PEG), can be cleaned successfully, including a known-age test.


Assuntos
Arqueologia , Datação Radiométrica , Navios , Datação Radiométrica/métodos , Calibragem , Arqueologia/métodos , Chipre , Radioisótopos de Carbono/análise , Teorema de Bayes
4.
J Labelled Comp Radiopharm ; 67(8): 288-294, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38803015

RESUMO

Carbon-14 labeling synthesis of RORγt inhibitor JNJ-61803534 (1) was accomplished in four steps with the C14 label located at the thiazole-2-carboxamide carbon. The synthesis featured a highly efficient conversion of nitrile [14C]-12 to ester [14C]-17 under mild conditions via an imidate intermediate, overcoming the unsuccessful direct hydrolysis of nitrile 12 under either acidic or basic conditions. Since carbon-14 labeling via [14C]-nitrile installation and subsequent conversion to [14C]-carboxylic acid derivatives is a common labeling strategy, an efficient conversion of a nitrile to an ester under mild conditions could be of use for the future C14 labeling syntheses.


Assuntos
Radioisótopos de Carbono , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Radioisótopos de Carbono/química , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Marcação por Isótopo , Técnicas de Química Sintética , Tiazóis/síntese química , Tiazóis/química , Tiazóis/farmacologia
5.
Magn Reson Imaging ; 111: 148-156, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38729226

RESUMO

PURPOSE: Magnetization transfer ratio asymmetry (MTRasym) analysis is used for chemical exchange saturation transfer (CEST) in patients with gliomas; however, this approach has limitations. CEST imaging using a multi-pool model (MPM) may allow a more detailed assessment of gliomas; however, its mechanism remains unknown. This study aimed to assess the relationship between CEST imaging by MPM, intravoxel incoherent motion (IVIM), and 11C-methionine (11C-MET) uptake on positron emission tomography/computed tomography (PET/CT) to clarify the clinical significance of CEST imaging using MPM in gliomas. METHODS: This retrospective study included 17 patients with gliomas who underwent 11C-MET PET/CT at our institution between January 2020 and January 2022. Two-dimensional axial CEST imaging was conducted using single-shot fast-spin echo acquisition at 3 T. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), f, MTRasym (3.5 ppm), parameters of MPM-based CEST imaging, and tumor-to-contralateral normal brain tissue (T/N) ratio were calculated using a region-of-interest analysis. Shapiro-Wilk test, weighted kappa coefficient, and Spearman's rank correlation coefficients were used for statistical analysis. RESULTS: Significant correlations were found between APT_T1 and T/N ratio (ρ = 0.87, p < 0.001), APT_T2 and T/N ratio (ρ = 0.47, p < 0.05), MTRasym and T/N ratio (ρ = 0.55, p < 0.01), and T2/T1 and T/N ratio (ρ = -0.36, p < 0.05). Furthermore, significant correlations were observed between APT_T1 and ADC (ρ = -0.67, p < 0.001), APT_T1 and D (ρ = -0.70, p < 0.001), APT_T2 and D* (ρ = -0.45, p < 0.05), and T2/T1 and D (ρ = 0.39, p < 0.05). CONCLUSION: These preliminary findings indicate that MPM-based CEST imaging parameters correlate with IVIM and 11C-MET uptake on PET/CT in patients with gliomas. In particular, the new parameter APT_T1 correlated more strongly with 11C-MET uptake compared to the traditional CEST parameter MTRasym.


Assuntos
Neoplasias Encefálicas , Glioma , Imageamento por Ressonância Magnética , Metionina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Glioma/diagnóstico por imagem , Glioma/metabolismo , Masculino , Feminino , Metionina/farmacocinética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Estudos Retrospectivos , Adulto , Imageamento por Ressonância Magnética/métodos , Idoso , Movimento (Física) , Radioisótopos de Carbono/farmacocinética , Processamento de Imagem Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo
6.
J Labelled Comp Radiopharm ; 67(7): 254-262, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703027

RESUMO

Reductive N-11C-methylation using [11C]formaldehyde and amines has been used to prepare N-11C-methylated compounds. However, the yields of the N-11C-methylated compounds are often insufficient. In this study, we developed an efficient method for base-free reductive N-11C-methylation that is applicable to a wide variety of substrates, including arylamines bearing electron-withdrawing and electron-donating substituents. A 2-picoline borane complex, which is a stable and mild reductant, was used. Dimethyl sulfoxide was used as the primary reaction solvent, and glacial acetic acid or aqueous acetic acid was used as a cosolvent. While reductive N-11C-methylation efficiently proceeded under anhydrous conditions in most cases, the addition of water to the reductive N-11C-methylation generally increased the yield of the N-11C-methylated compounds. Substrates with hydroxy, carboxyl, nitrile, nitro, ester, amide, and phenone moieties and amine salts were applicable to the reaction. This proposed method for reductive N-11C-methylation should be applicable to a wide variety of substrates, including thermo-labile and base-sensitive compounds because the reaction was performed under relatively mild conditions (70°C) without the need for a base.


Assuntos
Aminas , Radioisótopos de Carbono , Formaldeído , Hidrocarbonetos Iodados , Metilação , Radioisótopos de Carbono/química , Aminas/química , Formaldeído/química , Hidrocarbonetos Iodados/química , Oxirredução
7.
J Labelled Comp Radiopharm ; 67(7): 263-272, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38711257

RESUMO

Rimsulfuron is a sulfonylurea herbicide that controls grass and broadleaf weeds in maize, potatoes, fruits, nuts, and other crops. It can also be used as a burndown herbicide to clear invasive weed species along roadsides and other nonagricultural land. Rimsulfuron acts as an acetolactase synthase (ALS) inhibitor, blocking the synthesis of essential amino acids required for plant growth. As is common practice, rimsulfuron has been subject to periodic reviews by regulatory agencies for reregistration since its introduction into the market in the early 1990s. The goal of these reviews is to ensure that the herbicide carries out its intended use without creating adverse side effects to humans and the environment. Since scientific methods are continually evolving and being developed, global regulatory agencies can require additional studies to address data gaps for pesticide renewals. During this reregistration process for rimsulfuron, a new confined rotational crop study was required to address a data gap requested by the European Food Safety Authority (EFSA). Consequently, the corresponding pyridine and pyrimidine radiolabeled [14C]rimsulfuron and [M + 3] stable isotopes of rimsulfuron were synthesized for this study to support the reregistration process.


Assuntos
Radioisótopos de Carbono , Produtos Agrícolas , Marcação por Isótopo , Piridinas , Radioisótopos de Carbono/química , Produtos Agrícolas/metabolismo , Piridinas/química , Piridinas/síntese química , Herbicidas/síntese química , Herbicidas/química , Sulfonamidas
8.
New Phytol ; 243(1): 398-406, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38757767

RESUMO

The minute 'dust seeds' of some terrestrial orchids preferentially germinate and develop as mycoheterotrophic protocorms near conspecific adult plants. Here we test the hypothesis that mycorrhizal mycelial connections provide a direct pathway for transfer of recent photosynthate from conspecific green orchids to achlorophyllous protocorms. Mycelial networks of Ceratobasidium cornigerum connecting green Dactylorhiza fuchsii plants with developing achlorophyllous protocorms of the same species were established on oatmeal or water agar before the shoots of green plants were exposed to 14CO2. After incubation for 48 h, the pattern of distribution of fixed carbon was visualised in intact entire autotrophic/protocorm systems using digital autoradiography and quantified in protocorms by liquid scintillation counting. Both methods of analysis revealed accumulation of 14C above background levels in protocorms, confirming that autotrophic plants supply carbon to juveniles via common mycorrhizal networks. Despite some accumulation of plant-fixed carbon in the fungal mycelium grown on oatmeal agar, a greater amount of carbon was transferred to protocorms growing on water agar, indicating that the polarity of transfer may be influenced by sink strength. We suggest this transfer pathway may contribute significantly to the pattern and processes determining localised orchid establishment in nature, and that 'parental nurture' via common mycelial networks may be involved in these processes.


Assuntos
Processos Autotróficos , Processos Heterotróficos , Micorrizas , Orchidaceae , Fotossíntese , Micorrizas/fisiologia , Orchidaceae/microbiologia , Micélio , Carbono/metabolismo , Radioisótopos de Carbono
10.
ESMO Open ; 9(5): 103448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38718704

RESUMO

BACKGROUND: The early identification of responsive and resistant patients to androgen receptor-targeting agents (ARTA) in metastatic castration-resistant prostate cancer (mCRPC) is not completely possible with prostate-specific antigen (PSA) assessment and conventional imaging. Considering its ability to determine metabolic activity of lesions, positron emission tomography (PET) assessment might be a promising tool. PATIENTS AND METHODS: We carried out a monocentric prospective study in patients with mCRPC treated with ARTA to evaluate the role of different PET radiotracers: 49 patients were randomized to receive 11C-Choline, Fluorine 18 fluciclovine (anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid - FACBC) (18F-FACBC), or Gallium-68-prostate-specific-membrane-antigen (68Ga-PSMA) PET, one scan before therapy and one 2 months later. The primary aim was to investigate the performance of three novel PET radiotracers for the early evaluation of response to ARTA in metastatic CRPC patients; the outcome evaluated was biochemical response (PSA reduction ≥50%). The secondary aim was to investigate the prognostic role of several semiquantitative PET parameters and their variations with the different radiotracers in terms of biochemical progression-free survival (bPFS) and overall survival (OS). The study was promoted by the Italian Department of Health (code RF-2016-02364809). RESULTS: Regarding the primary endpoint, at log-rank test a statistically significant correlation was found between metabolic tumor volume (MTV) (P = 0.018) and total lesion activity (TLA) (P = 0.025) percentage variation among the two scans with 68Ga-PSMA PET and biochemical response. As for the secondary endpoints, significant correlations with bPFS were found for 68Ga-PSMA total MTV and TLA at the first scan (P = 0.001 and P = 0.025, respectively), and MTV percentage variation (P = 0.031). For OS, statistically significant correlations were found for different 68Ga-PSMA and 18F-FACBC parameters and for major maximum standardized uptake value at the first 11C-Choline PET scan. CONCLUSIONS: Our study highlighted that 11C-Choline, 68Ga-PSMA, and 18F-FACBC semiquantitative PET parameters and their variations present a prognostic value in terms of OS and bPFS, and MTV and TLA variations with 68Ga-PSMA PET a correlation with biochemical response, which could help to assess the response to ARTA.


Assuntos
Radioisótopos de Carbono , Ácidos Carboxílicos , Colina , Ciclobutanos , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Prospectivos , Idoso , Ácidos Carboxílicos/farmacologia , Ácidos Carboxílicos/uso terapêutico , Radioisótopos de Gálio/farmacologia , Colina/farmacologia , Ciclobutanos/farmacologia , Ciclobutanos/uso terapêutico , Radioisótopos de Carbono/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Pessoa de Meia-Idade , Isótopos de Gálio , Compostos Radiofarmacêuticos/farmacologia , Idoso de 80 Anos ou mais , Receptores Androgênicos/metabolismo
11.
World J Gastroenterol ; 30(17): 2302-2307, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38813047

RESUMO

In this editorial, we discuss the article in the World Journal of Gastroenterology. The article conducts a meta-analysis of the diagnostic accuracy of the urea breath test (UBT), a non-invasive method for detecting Helicobacter pylori (H. pylori) infection in humans. It is based on radionuclide-labeled urea. Various methods, both invasive and non-invasive, are available for diagnosing H. pylori infection, including endoscopy with biopsy, serology for immunoglobulin titers, stool antigen analysis, and UBT. Several guidelines recommend UBTs as the primary choice for diagnosing H. pylori infection and for reexamining after eradication therapy. It is used to be the first choice non-invasive test due to their high accuracy, specificity, rapid results, and simplicity. Moreover, its performance remains unaffected by the distribution of H. pylori in the stomach, allowing a high flow of patients to be tested. Despite its widespread use, the performance characteristics of UBT have been inconsistently described and remain incompletely defined. There are two UBTs available with Food and Drug Administration approval: The 13C and 14C tests. Both tests are affordable and can provide real-time results. Physicians may prefer the 13C test because it is non-radioactive, compared to 14C which uses a radioactive isotope, especially in young children and pregnant women. Although there was heterogeneity among the studies regarding the diagnostic accuracy of both UBTs, 13C-UBT consistently outperforms the 14C-UBT. This makes the 13C-UBT the preferred diagnostic approach. Furthermore, the provided findings of the meta-analysis emphasize the significance of precise considerations when choosing urea dosage, assessment timing, and measurement techniques for both the 13C-UBT and 14C-UBT, to enhance diagnostic precision.


Assuntos
Testes Respiratórios , Dispepsia , Infecções por Helicobacter , Helicobacter pylori , Ureia , Adulto , Humanos , Testes Respiratórios/métodos , Isótopos de Carbono/análise , Radioisótopos de Carbono , Dispepsia/microbiologia , Dispepsia/diagnóstico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/imunologia , Sensibilidade e Especificidade , Ureia/análise , Ureia/metabolismo , Metanálise como Assunto
12.
World Neurosurg ; 186: e495-e505, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583563

RESUMO

OBJECTIVE: To clarify the relationships between 11C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification. METHODS: A total of 125 newly diagnosed patients with ADG were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal background ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the patients with ADG. We also evaluated the prognoses of the 93 surgically treated patients. RESULTS: The patients with isocitrate dehydrogenase wild ADG showed significantly higher MET-PET metrics (P < 0.05 for all parameters), significantly shorter overall survival and progression-free survival (P < 0.0001 for both) than those of the patients with isocitrate dehydrogenase mutant (IDHm) ADG. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in patients with IDHm grade (G) 4 astrocytoma than patients with IDHm G2/3 astrocytoma (P < 0.05 for all), but not than patients with G2-3 oligodendroglioma. The progression-free survival was significantly shorter in the patients with G4 astrocytoma versus the patients with G2/3 astrocytoma and G3 oligodendroglioma (P < 0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than nonrecurrent patients (P < 0.01 for both), but no significant differences were found in MTV or TLMU values. CONCLUSIONS: MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR.


Assuntos
Neoplasias Encefálicas , Glioma , Isocitrato Desidrogenase , Metionina , Tomografia por Emissão de Pósitrons , Organização Mundial da Saúde , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/patologia , Prognóstico , Idoso , Isocitrato Desidrogenase/genética , Adulto Jovem , Radioisótopos de Carbono , Estudos Retrospectivos , Carga Tumoral
13.
J Agric Food Chem ; 72(18): 10579-10583, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38683941

RESUMO

A 14C-based method was developed to study the rate and extent of covalent bond formation between ß-lactoglobulin and three model flavor compounds: a ketone (2-undecanone UDO), an aldehyde (decanal DAL), an isothiocyanate (2-phenylethyl isothiocyanate PEITC), and an unreactive "methods blank" (decane DEC). Aqueous protein solutions with one of the 14C-labeled model flavor compounds were placed in water baths at 25, 45, and 65 °C for 4 weeks measuring the amount of flavor: protein reaction at 1, 3, 7, 14, 21, and 28 days. UDO showed lowest reactivity (max of 0.9% of added compound reacted), DAL (max of 16.4% reacted), and PEITC (max of 71.8% reacted). All compounds showed a rapid initial reaction rate which slowed after ca. 7 days. It appears that only PEITC (at 65 °C) saturated all potential protein-reactive sites over the storage period.


Assuntos
Aromatizantes , Lactoglobulinas , Aldeídos/química , Radioisótopos de Carbono/análise , Radioisótopos de Carbono/química , Aromatizantes/química , Isotiocianatos/química , Cetonas/química , Cinética , Lactoglobulinas/química
14.
J Neurooncol ; 168(2): 355-365, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38557927

RESUMO

PURPOSE: The proximate localization of MTAP, which encodes methylthioadenosine phosphorylase, and CDKN2A/B on Chromosome 9q21 has allowed the loss of MTAP expression as a surrogate for homozygous deletion of CDKN2A/B. This study aimed to determine whether MTAP status correlates with clinical outcomes and 11C-methionine uptake in astrocytomas with IDH mutations. METHODS: We conducted immunohistochemistry for MTAP in 30 patients with astrocytoma, IDH-mutant who underwent 11C-methionine positron emission tomography scans prior to surgical resection. The tumor-to-normal (T/N) ratio of 11C-methionine uptake was calculated using the mean standardized uptake value (SUV) for tumor and normal brain tissues. Cox regression analysis was used for multivariate survival analysis. RESULTS: Among IDH-mutant astrocytomas, 26.7% (8/30) exhibited the loss of cytoplasmic MTAP expression, whereas 73.3% (22/30) tumors retained MTAP expression. The median progression-free survival (PFS) was significantly shorter in patients with MTAP loss than those with MTAP retention (1.88 years vs. 6.80 years, p = 0.003). The median overall survival (OS) was also shorter in patients with MTAP loss than in MTAP-retaining counterparts (5.23 years vs. 10.69 years, p = 0.019). Multivariate analysis identified MTAP status (hazard ratio (HR), 0.081) and extent of resection (HR, 0.104) as independent prognostic factors for PFS. Astrocytomas lacking cytoplasmic MTAP expression showed a significantly higher median T/N ratio for 11C-methionine uptake than tumors retaining MTAP (2.12 vs. 1.65, p = 0.012). CONCLUSION: Our study revealed that the loss of MTAP expression correlates with poor prognosis and an elevated T/N ratio of 11C-methionine uptake in astrocytoma, IDH-mutant.


Assuntos
Astrocitoma , Neoplasias Encefálicas , Isocitrato Desidrogenase , Metionina , Mutação , Purina-Núcleosídeo Fosforilase , Humanos , Purina-Núcleosídeo Fosforilase/metabolismo , Purina-Núcleosídeo Fosforilase/genética , Astrocitoma/genética , Astrocitoma/metabolismo , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Astrocitoma/mortalidade , Feminino , Masculino , Metionina/metabolismo , Pessoa de Meia-Idade , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/mortalidade , Prognóstico , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Adulto , Idoso , Tomografia por Emissão de Pósitrons , Radioisótopos de Carbono , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Adulto Jovem
15.
ACS Chem Neurosci ; 15(9): 1882-1892, 2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38634759

RESUMO

The sphingosine-1-phosphate receptor 1 (S1PR1) radiotracer [11C]CS1P1 has shown promise in proof-of-concept PET imaging of neuroinflammation in multiple sclerosis (MS). Our HPLC radiometabolite analysis of human plasma samples collected during PET scans with [11C]CS1P1 detected a radiometabolite peak that is more lipophilic than [11C]CS1P1. Radiolabeled metabolites that cross the blood-brain barrier complicate quantitative modeling of neuroimaging tracers; thus, characterizing such radiometabolites is important. Here, we report our detailed investigation of the metabolite profile of [11C]CS1P1 in rats, nonhuman primates, and humans. CS1P1 is a fluorine-containing ligand that we labeled with C-11 or F-18 for preclinical studies; the brain uptake was similar for both radiotracers. The same lipophilic radiometabolite found in human studies also was observed in plasma samples of rats and NHPs for CS1P1 labeled with either C-11 or F-18. We characterized the metabolite in detail using rats after injection of the nonradioactive CS1P1. To authenticate the molecular structure of this radiometabolite, we injected rats with 8 mg/kg of CS1P1 to collect plasma for solvent extraction and HPLC injection, followed by LC/MS analysis of the same metabolite. The LC/MS data indicated in vivo mono-oxidation of CS1P1 produces the metabolite. Subsequently, we synthesized three different mono-oxidized derivatives of CS1P1 for further investigation. Comparing the retention times of the mono-oxidized derivatives with the metabolite observed in rats injected with CS1P1 identified the metabolite as N-oxide 1, also named TZ82121. The MS fragmentation pattern of N-oxide 1 also matched that of the major metabolite in rat plasma. To confirm that metabolite TZ82121 does not enter the brain, we radiosynthesized [18F]TZ82121 by the oxidation of [18F]FS1P1. Radio-HPLC analysis confirmed that [18F]TZ82121 matched the radiometabolite observed in rat plasma post injection of [18F]FS1P1. Furthermore, the acute biodistribution study in SD rats and PET brain imaging in a nonhuman primate showed that [18F]TZ82121 does not enter the rat or nonhuman primate brain. Consequently, we concluded that the major lipophilic radiometabolite N-oxide [11C]TZ82121, detected in human plasma post injection of [11C]CS1P1, does not enter the brain to confound quantitative PET data analysis. [11C]CS1P1 is a promising S1PR1 radiotracer for detecting S1PR1 expression in the CNS.


Assuntos
Encéfalo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Humanos , Tomografia por Emissão de Pósitrons/métodos , Ratos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Compostos Radiofarmacêuticos/farmacocinética , Masculino , Receptores de Esfingosina-1-Fosfato/metabolismo , Ratos Sprague-Dawley , Radioisótopos de Flúor , Radioisótopos de Carbono
16.
J Labelled Comp Radiopharm ; 67(7): 273-276, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38641899

RESUMO

Mitochondrial membrane translocator protein 18 kDa (TSPO) expression is increased in activated microglia, established as a plausible target of neuroinflammation imaging. [11C]ER176, specifically binding to TSPO, has been developed as the third generation of radioligand for PET imaging of TSPO, which showed the potential in better quantifying neuroinflammation than its predecessors. In the current study, we developed an automated radiosynthesis with an improved HPLC purification method for [11C]ER176 clinical production. The improved HPLC separation was integrated into the automated production of [11C]ER176 using a reverse phase semi-preparative HPLC column with an isocratic pump and the mixture of methanol and 50 mM ammonium acetate as the mobile phase. The fraction corresponding to [11C]ER176 was collected around 8.5-9.0 min without the risk of getting contaminations from nearby impurities. The automated production process took about 30 min after end of bombardment (EOB) and the quality of the final product [11C]ER176 met all specifications for clinical use based on current US Pharmacopeia and FDA CGMP requirements.


Assuntos
Compostos Radiofarmacêuticos , Receptores de GABA , Cromatografia Líquida de Alta Pressão/métodos , Receptores de GABA/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Radioisótopos de Carbono/química , Ligantes , Humanos , Radioquímica
17.
Environ Pollut ; 350: 124050, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677454

RESUMO

Identifying the sources of polycyclic aromatic hydrocarbons (PAHs) in complex environmental matrices is essential for understanding the impact of combustion-related human activities on the environment. Since the turn of the century, advances in analytical capability and accuracy of accelerator mass spectrometry (AMS) have made it possible to accurately determine the source apportionment of PAHs based on their radiocarbon (14C) mass conservation. This also allows us to trace the environmental transport processes of PAHs from the perspective of molecular 14C. However, natural environmental matrices have very low concentrations of PAHs (ppb to ppm level). To meet the requirements of carbon weight for 14C measurement by AMS, trace PAHs in complex environmental matrices must be enriched thousands of times, and then higher purity individual PAH molecules should be obtained through a series of complex purification procedures. Therefore, the technical difficulty is the main challenge in expanding the application of compound-specific 14C analysis in environmental science. This article reviews the detailed pretreatment procedures for 14C measurement of specific PAHs, including sample enrichment, extraction and purification of aromatic components, preparation of compound-specific PAHs by preparative capillary gas chromatography, graphitization of samples with ultra-small carbon content, and relevant quality control and assurance procedures. This study aims to help environmental geoscientists understand the technical process of 14C analysis of PAHs and inspire new scientific questions related to environmental science. To our knowledge, this is the first comprehensive review of the technical method of compound-specific 14C analysis for PAHs.


Assuntos
Radioisótopos de Carbono , Monitoramento Ambiental , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Monitoramento Ambiental/métodos , Radioisótopos de Carbono/análise , Poluentes Ambientais/análise
18.
Toxicol In Vitro ; 98: 105835, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679218

RESUMO

Octocrylene is a common sun filter ingredient used to protect the skin from damaging UV rays. Benzophenone is an impurity found in formulations containing octocrylene. [14C]-Benzophenone was spiked (0.1 g/L) into 2 commercial sunscreen formulations; Neutrogena® Beach Defense Sunscreen Spray Broad Spectrum SPF 70 Aerosol, Neutrogena® Ultra Sheer Body Mist Sunscreen Broad Spectrum SPF 30 Aerosol, and an acetone vehicle. The formulations were applied (ca 2 µL/cm2) to dermatomed human skin mounted in static diffusion cells in vitro. Receptor fluid was collected up to 24 h post dose. All samples were analyzed by liquid scintillation counting. The dermal delivery of [14C]-Benzophenone was 10.02, 9.04 and 5.19% for the 3 formulations. However, the [14C]-Benzophenone mass balances were low; 81.5, 85.3 and 8.02%, respectively. A volatility test was performed replacing skin with aluminum foil for the sunscreen formulations only. The [14C]-Benzophenone mass balance at dosing was 99% but fell to 56.9 and 60.6% at 24 h post dose, confirming the losses were due to [14C]-Benzophenone volatility. A conservative dermal absorption value of 12.42% was proposed to cover [14C]-Benzophenone containing formulations.


Assuntos
Benzofenonas , Radioisótopos de Carbono , Absorção Cutânea , Pele , Protetores Solares , Benzofenonas/farmacocinética , Benzofenonas/administração & dosagem , Humanos , Protetores Solares/farmacocinética , Protetores Solares/química , Protetores Solares/administração & dosagem , Pele/metabolismo , Técnicas In Vitro , Acrilatos/química , Acrilatos/farmacocinética
19.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38673791

RESUMO

Agriculture in the 21st century faces many formidable challenges with the growing global population. Increasing demands on the planet's natural resources already tax existing agricultural practices. Today, many farmers are using biochemical treatments to improve their yields. Commercialized organic biostimulants exist in the form of pyroligneous acid generated by burning agricultural waste products. Recently, we examined the mechanisms through which a commercial pyroligneous acid product, Coriphol™, manufactured by Corigin Solutions, Inc., stimulates plant growth. During the 2023 growing season, outdoor studies were conducted in soybean to examine the effects of different Coriphol™ treatment concentrations on plant growth. Plant height, number of leaves, and leaf size were positively impacted in a dose-dependent manner with 2 gallon/acre soil treatments being optimal. At harvest, this level of treatment boosted crop yield by 40%. To gain an understanding of why Coriphol™ improves plant fitness, follow-up laboratory-based studies were conducted using radiocarbon flux analysis. Here, radioactive 11CO2 was administered to live plants and comparisons were made between untreated soybean plants and plants treated at an equivalent Coriphol™ dose of 2 gallons/acre. Leaf metabolites were analyzed using radio-high-performance liquid chromatography for [11C]-chlorophyll (Chl) a and b components, as well as [11C]-ß-carotene (ß-Car) where fractional yields were used to calculate metabolic rates of synthesis. Altogether, Coriphol™ treatment boosted rates of Chl a, Chl b, and ß-Car biosynthesis 3-fold, 2.6-fold, and 4.7-fold, respectively, and also increased their metabolic turnover 2.2-fold, 2.1-fold, and 3.9-fold, respectively. Also, the Chl a/b ratio increased from 3.1 to 3.4 with treatment. Altogether, these effects contributed to a 13.8% increase in leaf carbon capture.


Assuntos
Glycine max , Folhas de Planta , Glycine max/metabolismo , Glycine max/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Radioisótopos de Carbono , Desenvolvimento Vegetal , Solo/química , Clorofila/metabolismo
20.
J Labelled Comp Radiopharm ; 67(5): 180-185, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38605481

RESUMO

Velagliflozin is the active ingredient of the first oral liquid medication approved by the Food and Drug Administration for the treatment of diabetes in cats. This compound belongs to the known class of sodium-glucose cotransporter 2 inhibitors approved to treat diabetes in human. Here, we report the detailed synthesis of velagliflozin labeled with carbon 14 and carbon 13.


Assuntos
Isótopos de Carbono , Radioisótopos de Carbono , Radioisótopos de Carbono/química , Isótopos de Carbono/química , Técnicas de Química Sintética , Glucosídeos/síntese química , Glucosídeos/química , Glucosídeos/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/síntese química , Inibidores do Transportador 2 de Sódio-Glicose/química , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Compostos Benzidrílicos
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