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1.
J Chem Phys ; 160(16)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38647312

RESUMO

Understanding and further regulating the degradation of mandrel materials is a key aspect of target fabrication in inertial confinement fusion (ICF). Here, a quasi-one-dimensional confinement model is developed using a series of single-walled carbon nanotubes with varying diameters (Dm), and the degradation of poly-α-methylstyrene (PAMS) as a typical mandrel material is investigated under such confined conditions by using the combined method of quantum mechanics and molecular mechanics. In comparison to the isolated system, the calculations show that confinement can decrease or increase the energy barriers of PAMS degradation, which directly depends on Dm. Following which a clear exponential relationship between the degradation rate of PAMS and its own density is derived, indicating that the density of PAMS can be used to regulate mandrel degradation. This work highlights the important effects of confinement on degradation and provides a valuable reference for further development of polymer degradation technologies in ICF target fabrication and other fields.

2.
Eur J Nucl Med Mol Imaging ; 51(7): 2012-2022, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38326656

RESUMO

PURPOSE: Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study. METHODS: [18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET. RESULTS: The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers. CONCLUSION: [18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan.


Assuntos
Fluordesoxiglucose F18 , Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Animais , Camundongos , Fluordesoxiglucose F18/farmacocinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Masculino , Feminino , Linhagem Celular Tumoral , Células HEK293 , Distribuição Tecidual , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacocinética , Idoso , Proteínas de Membrana , Endopeptidases
3.
BMC Med Imaging ; 24(1): 11, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172764

RESUMO

BACKGROUND: To validate the feasibility of water enema PET/CT (WE-PET/CT) in incidental colorectal 18F-FDG uptake and improve the accuracy of diagnosing colorectal neoplastic lesions. METHODS: We retrospectively analysed the electronic records of 338 patients undergoing common PET/CT and WE-PET/CT at our hospital. PET/CT results were correlated with colonoscopy pathology and follow-up results. The ROC contrast curve was plotted to evaluate the accuracy of SUVmax on common PET/CT and WE-PET/CT for detecting neoplastic lesions. SUVmax and the median retention indexes (RIs) of cancerous, precancerous, and benign lesions and physiologic uptake were compared. RESULTS: The sensitivity, specificity and accuracy of diagnosing neoplastic lesions with common PET/CT were 84.0%, 78.3% and 80.2%, respectively. The corresponding results with WE-PET/CT were 95.8%, 96.5% and 96.2%. The AUC of SUVmax on WE-PET/CT was significantly higher than that on common PET/CT (0.935 vs. 0.524, p < 0.001). The median SUVmax on WE-PET/CT was significantly higher than that on common PET/CT in cancerous and precancerous lesions, and significantly decreased in benign lesions and physiologic uptake (p < 0.001). The RI was significantly different between cancerous lesions and physiologic uptake, between precancerous lesions and physiologic uptake, between benign lesions and physiologic uptake, and between cancerous and benign lesions (p < 0.05). CONCLUSIONS: WE-PET/CT is a noninvasive, well-tolerated and effective technique for diagnosing incidental colorectal 18F-FDG uptake. It is helpful for a timely colonoscopy and can effectively avoid an unnecessary colonoscopy for incidental colorectal 18F-FDG uptake.


Assuntos
Neoplasias Colorretais , Lesões Pré-Cancerosas , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Água , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Achados Incidentais , Neoplasias Colorretais/diagnóstico , Enema
4.
Front Oncol ; 13: 1106890, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910656

RESUMO

Occult breast cancer is an uncommon type of breast cancer and its diagnosis is challenging. It is usually invisible on multiple imaging examines. Metastases to the rectum and inguinal lymph nodes from occult breast lobular cancer are even rarer. 68Ga-DOTA peptides can image neuroendocrine tumors by targeting specific somatostatin receptors. Besides, other tumors, including breast cancer, have been shown to express somatostatin receptors. In this case, we presented a 63-year-old woman who underwent both 18F-FDG and 68Ga-DOTATATE PET/CT due to a rectal polyp. An endoscopic excision biopsy confirmed metastatic carcinoma of suspected breast origin, but subsequent ultrasound and MRI showed no signs of malignancy in the breast and adnexa uteri. PET/CT showed obvious 68Ga-DOTATATE activity in bilateral axillary and right inguinal lymph nodes with mild 18F-FDG uptake. Final histopathology at the left axillary, right inguinal lymph nodes, and rectum indicated metastases from breast cancer while the origin remained radiologically occult. Additionally, one uterine fibroids was found with positive uptake of 68Ga-DOTATATE and negative uptake of 18F-FDG. This case suggested that 68Ga-DOTATAE PET/CT may be an effective supplement in diagnosing OBC lymph node metastases with mild 18F-FDG uptake, and it may provide a new technology for the clinical diagnosis of occult breast cancer.

5.
Phys Chem Chem Phys ; 24(41): 25420-25425, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36250547

RESUMO

The exploration of mandrel materials with superior degradation performance to the traditionally adopted hydrocarbon polymer of poly-α-methylstyrene (PAMS), has always been an important pursuit for fabricating high-quality inertial confinement fusion (ICF) targets. Here, we propose a method to enhance the degradation performance of mandrel material based on side-chain engineering. A series of hydrocarbon cyclic functional groups, including cyclopentane, cyclopentadiene, naphthalene and azulene, are used to replace the benzene ring on the side chain of PAMS to form new polymer structures. The results show that the degradation performance of structures can be largely regulated by different side chains. In particular, one of the naphthalene-substituted structures has similar properties to PAMS, but the required degradation condition is lower. Furthermore, the reaction rate calculations indicate that this structure is expected to be synthesized experimentally. This work provides a direction for side-chain engineering for research into the key technology of ICF target fabrication in the future.

6.
iScience ; 25(8): 104733, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35880049

RESUMO

Poly-α-methylstyrene (PAMS), as an ideal mandrel material used in the fabrication of inertial confinement fusion (ICF) targets, its efficient degradation is the key to the quality of targets. However, there is a great challenge to achieve enhanced degradation. Here, we proposed the strategy to optimize the degradation of PAMS microspheres using di-tert-butyl peroxide (DTBP) as a degradation initiator. Experimentally, monodisperse PAMS microspheres with DTBP were controllably prepared by a microfluidic-based microencapsulation technique. Thermogravimetric results show that DTBP largely decreases the initial degradation temperature from 550 K to 450 K, which effectively promotes the thermal degradation of PAMS microspheres. Theoretically, DTBP can reduce the activation energy of degradation. Moreover, the potential energy surfaces were used to describe the degradation process at the atomic level. Our work brings a new direction for the study of mandrel degradation in ICF targets fabrication, and also provides a valuable reference for solving the pollution of waste plastics.

7.
iScience ; 25(1): 103674, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35024593

RESUMO

Poly-α-methylstyrene (PAMS) is considered as the preferred mandrel material, whose degradation is crucial for the fabrication of high-quality inertial confinement fusion (ICF) targets. Herein, we reveal that hydrogen atom transfer (HAT) during PAMS degradation, which is usually attributed to the thermal effect, unexpectedly exhibits a strong high-temperature tunneling effect. Specifically, although the energy barrier of the HAT reaction is only 10-2 magnitude different from depolymerization, the tunneling probability of the former can be 14-32 orders of magnitude greater than that of the latter. Furthermore, chain scission following HAT will lead to a variety of products other than monomers. Our work highlights that quantum tunneling may be an important source of uncertainty in PAMS degradation, which will provide a direction for the further development of key technology of target fabricating in ICF research and even the solution of plastic pollution.

8.
Phys Rev Lett ; 127(24): 245001, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34951808

RESUMO

In inertial confinement approaches to fusion, the asymmetry of target implosion is a major obstacle to achieving high gain in the laboratory. A recently proposed octahedral spherical hohlraum makes it possible to naturally create spherical target irradiation without supplementary symmetry control. Before any decision is made to pursue an ignition-scale laser system based on the octahedral hohlraum, one needs to test the concept with the existing facilities. Here, we report a proof-of-concept experiment for the novel octahedral hohlraum geometry on the cylindrically configured SGIII laser facility without a symmetry control. All polar and equatorial self-emission images of the compressed target show a near round shape of convergence ratio 15 under both square and shaped laser pulses. The observed implosion performances agree well with the ideal spherical implosion simulation. It also shows limitations with using the existing facilities and adds further weight to the need to move to a spherical port geometry for future ignition laser facilities.

9.
Nucl Med Biol ; 98-99: 76-83, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34062322

RESUMO

PURPOSE: To evaluate the potential feasibility of Al[18F]F-1,4,7-triazacyclononane-1,4,7-triaceticacid (NOTA)-tripolyethylene glycol (PEG3)-Duramycin (Al[18F]F-NOTA-PEG3-Duramycin) positron emission tomography (PET) for imaging of rat hepatic fibrosis. PROCEDURES: Hepatic fibrosis rat models were injected with thioacetamide (TAA), control rats received saline (n = 12 per group). Rats in the two groups underwent PET imaging using Al[18F]F-NOTA-PEG3-Duramycin and [18F]FDG at multiple time points (2, 4, 6, and 8 weeks after TAA or saline treatment). Between-group differences in the apoptosis rate, fibrotic activity, and liver uptake of Al[18F]F-NOTA-PEG3-Duramycin or [18F]FDG were assessed using Student's t-test. Imaging results were cross-validated using histopathology detection and Pearson's correlation test was used to assess the association relationships between radioactive uptake value and quantified histopathological data. RESULTS: Compared with control group at multiple time points, each TAA group showed a higher radioactive liver uptake of Al[18F]F-NOTA-PEG3-Duramycin (each P < 0.05). Furthermore, the increase in the liver uptake of Al[18F]F-NOTA-PEG3-Duramycin was proportional to the progression of fibrosis (R2 = 0.8846, P < 0.001) and apoptosis rate (R2 = 0.9208, P < 0.001) in the TAA group. Meanwhile, there were also between-group differences in [18F]FDG uptake in each phase (P < 0.05), however, no relationship between [18F]FDG uptake and the fibrotic activity was observed. CONCLUSIONS: Al[18F]F-NOTA-PEG3-Duramycin PET/CT could be applied to monitor the progression of liver fibrosis, whereas [18F]FDG PET/CT could not. Implications of this work for noninvasive diagnosis of liver fibrosis, assessment of fibrotic activity, and evaluation of antifibrotic therapy are expected.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Animais , Morte Celular , Humanos , Ratos
10.
Front Oncol ; 11: 645162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996562

RESUMO

Comparing MRI and histopathology, this study aims to comprehensively explore the potential application of 18F-trifluoromethylated D-cysteine (S-[18F]CF3-D-CYS) in evaluating glioma by using orthotopic C6 glioma models. Sprague-Dawley (SD) rats (n = 9) were implanted with C6 glioma cells. Tumor growth was monitored every week by multiparameter MRI [including dynamic contrast-enhanced MRI (DCE-MRI)], [18F]FDG, S-[18F]CF3-D-CYS, and [18F]FDOPA PET imaging. Repeated scans of the same rat with the two or three [18F]-labeled radiotracers were investigated. Initial regions of interest were manually delineated on T2WI and set on the same level of PET images, and tumor-to-normal brain uptake ratios (TNRs) were calculated to semiquantitatively assess the tracer accumulation in the tumor. The tumor volume in PET and histopathology was calculated. HE and Ki67 immunohistochemical staining were further performed. The correlations between the uptake of S-[18F]CF3-D-CYS and Ki67 were analyzed. Dynamic S-[18F]CF3-D-CYS PET imaging showed tumor uptake rapidly reached a peak, maintained plateau during 10-30 min after injection, then decreased slowly. Compared with [18F]FDG and [18F]FDOPA PET imaging, S-[18F]CF3-D-CYS PET demonstrated the highest TNRs (P < 0.05). There were no significant differences in the tumor volume measured on S-[18F]CF3-D-CYS PET or HE specimen. Furthermore, our results showed that the uptake of S-[18F]CF3-D-CYS was significantly positively correlated with tumor Ki67, and the poor accumulated S-[18F]CF3-D-CYS was consistent with tumor hemorrhage. There was no significant correlation between the S-[18F]CF3-D-CYS uptakes and the Ktrans values derived from DCE-MRI. In comparison with MRI and histopathology, S-[18F]CF3-D-CYS PET performs well in the diagnosis and evaluation of glioma. S-[18F]CF3-D-CYS PET may serve as a valuable tool in the clinical management of gliomas.

11.
Mol Imaging Biol ; 23(6): 836-845, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33876336

RESUMO

PURPOSE: This study aimed to evaluate the potential value of 2-[18F]fluoropropionic acid ([18F]FPA) for PET imaging of prostate cancer (PCa) and to explore the relationship between [18F]FPA accumulation and fatty acid synthase (FASN) levels in PCa models. The results of the first [18F]FPA PET study of a PCa patient are reported. PROCEDURES: The LNCaP, PC-3 cell lines with high FASN expression, and DU145 cell lines with low FASN expression were selected for cell culture. A PET imaging comparison of [18F]FDG and [18F]FPA was performed in LNCaP, PC-3, and DU145 tumors. Additionally, in vivo inhibition experiments in those models were conducted with orlistat. In a human PET study, a patient with PCa before surgery was examined with [18F]FPA PET and [18F]FDG PET. RESULTS: The uptake of [18F]FPA in the LNCaP and PC-3 tumors was higher than that of [18F]FDG (P<0.05 and P<0.05), but was lower in DU145 tumors (P<0.05). The accumulation (% ID/g) of [18F]FPA in the LNCaP, PC-3, and DU145 tumors decreased by 27.6, 40.5, and 11.7 %, respectively, after treatment with orlistat. The [18F]FPA showed higher radioactive uptake than [18F]FDG in the first PCa patient. CONCLUSIONS: The [18F]FPA uptake in PCa models may be varies with fatty acid synthase activity and could be reduced after administration of a single FASN inhibitor, albeit the activity that is not measured directly. The [18F]FPA seems to be a potential broad-spectrum PET imaging agent and may serve as a valuable tool in the diagnosis of PCa in humans.


Assuntos
Propionatos , Neoplasias da Próstata , Linhagem Celular Tumoral , Humanos , Masculino , Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Próstata/metabolismo
12.
Appl Radiat Isot ; 168: 109530, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33285464

RESUMO

N-(2-18F-fluoropropionyl)-l-glutamate (18F-FPGLU), a new N-substituted 18F-labeling l-glutamate, is a potential amino acid tracer for oncology PET imaging with good tumor-to-background contrast in several tumor-bearing mice. Herein, we evaluated the potential value of 18F-FPGLU for PET imaging of glioma in orthotopic glioma-bearing SD rats. A series of competitive inhibition experiments with various types of inhibitors were conducted with C6 cells to investigate the transport mechanism of 18F-FPGLU in glioma. Establishment of orthotopic rat C6 glioma-bearing SD rats models was confirmed by MRI. Then PET imaging of 18F-FPGLU was performed on the orthotopic C6 glioma-bearing SD rats and compared with that of 18F-FDG. After the rats sacrificed, the whole brain was collected and immunofluorescence staining of glial fibrillary acidic protein (GFAP) and matrix metalloproteinase 2 (MMP2) were processed. Na+-dependent system XAG- and Na+-independent system XC- are the mainly transporters of 18F-FPGLU in C6 cells. N-methyl-d-aspartate (NMDA) receptor, which is associated with the invasiveness and proliferation of glioma cells, is also involved in the uptake of 18F-FPGLU. High uptake and retention of 18F-FPGLU was observerd in orthotopic glioma with good visualization and the tumor/background ratio reached 2.35 at 60 min post-injection, which was significantly higher than that of 18F-FDG (1.72) in small-animal PET images. High expression of MMP-2 and GFAP was observed in the immunofluorescence staining of glioma xerography slices. 18F-FPGLU seems to be a better potential PET tracer than 18F-FDG for brain glioma imaging with good visualization and ability to assess the tumor activity.


Assuntos
Encéfalo/diagnóstico por imagem , Radioisótopos de Flúor/química , Glioma/diagnóstico por imagem , Glutamatos/química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/química , Animais , Linhagem Celular Tumoral , Imunofluorescência , Glutamatos/farmacocinética , Xenoenxertos , Imageamento por Ressonância Magnética/métodos , Ratos , Ratos Sprague-Dawley
13.
BMC Plant Biol ; 20(1): 394, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847511

RESUMO

BACKGROUND: Tomatoes (Lycopersicon esculentum Mill) are key foods, and their molecular biology and evolution have been well described. Tomato plants originated in the tropics and, thus, are cold sensitive. RESULTS: Here, we generated LeGPA1 overexpressing and RNA-interference (RNAi) transgenic tomato plants, which we then used to investigate the function of LeGPA1 in response to cold stress. Functional LeGPA1 was detected at the plasma membrane, and endogenous LeGPA1 was highly expressed in the roots and leaves. Cold treatment positively induced the expression of LeGPA1. Overexpression of LeGPA1 conferred tolerance to cold conditions and regulated the expression of genes related to the INDUCER OF CBF EXPRESSION-C-REPEAT-BINDING FACTOR (ICE-CBF) pathway in tomato plants. In the LeGPA1-overexpressing transgenic plants, the superoxide dismutase, peroxidase, and catalase activities and soluble sugar and proline contents were increased, and the production of reactive oxygen species and membrane lipid peroxidation decreased under cold stress. CONCLUSIONS: Our findings suggest that improvements in antioxidant systems can help plants cope with the oxidative damage caused by cold stress, thereby stabilizing cell membrane structures and increasing the rate of photosynthesis. The data presented here provide evidence for the key role of LeGPA1 in mediating cold signal transduction in plant cells. These findings extend our knowledge of the roles of G-proteins in plants and help to clarify the mechanisms through which growth and development are regulated in processing tomato plants.


Assuntos
Aclimatação/genética , Aclimatação/fisiologia , Temperatura Baixa , Resposta ao Choque Frio/genética , Resposta ao Choque Frio/fisiologia , Solanum lycopersicum/genética , Solanum lycopersicum/fisiologia , China , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética
14.
BMC Med Imaging ; 20(1): 91, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746794

RESUMO

BACKGROUND: Secondary hyperparathyroidism (SHPT) usually requires parathyroidectomy when drug regimens fail. However, obtaining an exact preoperative map of the locations of the parathyroid glands is a challenge. The purpose of this study was to compare the diagnostic performance of US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT in patients with SHPT. METHODS: Sixty patients with SHPT who were undergoing dialysis were evaluated preoperatively by US, dual-phase 99mTc-MIBI scintigraphy, early and delayed 99mTc-MIBI SPECT/CT. Postoperative pathology served as the gold standard. The sensitivity, specificity, and accuracy were determined for each method. Spearman correlation analysis was used to analyse the correlation of hyperplastic parathyroid calcification with serum alkaline phosphatase (ALP) and parathyroid hormone (PTH). RESULTS: A total of 229 lesions in 60 patients were pathologically confirmed to be parathyroid hyperplasia, with 209 lesions in typical sites, 15 lesions in the upper mediastinum and 5 lesions in the thyroid. A total of 88.33% (53/60) of patients had four lesions. US, early and delayed 99mTc-MIBI SPECT/CT had significantly higher sensitivity and accuracy than dual-phase 99mTc-MIBI scintigraphy (P < 0.001). Furthermore, early 99mTc-MIBI SPECT/CT had significantly higher sensitivity (P < 0.001) and accuracy (P = 0.001 and P < 0.001) than US and delayed 99mTc-MIBI SPECT/CT. In patients with ectopic hyperplastic parathyroid glands, the sensitivity of early 99mTc-MIBI SPECT/CT (90%) was significantly higher than that of US (55%) and dual-phase 99mTc-MIBI scintigraphy (50%) (P < 0.05). The Spearman correlation results showed a significant albeit weak association between calcification and both serum PTH and ALP (P = 0.002). CONCLUSION: The ability of early 99mTc-MIBI SPECT/CT to detect hyperplastic parathyroid glands in patients with SHPT is superior to that of US, dual-phase 99mTc-MIBI scintigraphy and delayed 99mTc-MIBI SPECT/CT; furthermore, dual-phase 99mTc-MIBI SPECT/CT is not essential.


Assuntos
Hiperparatireoidismo Secundário/diagnóstico por imagem , Glândulas Paratireoides/diagnóstico por imagem , Compostos Radiofarmacêuticos/administração & dosagem , Insuficiência Renal Crônica/terapia , Tecnécio Tc 99m Sestamibi/administração & dosagem , Adulto , Fosfatase Alcalina/sangue , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/cirurgia , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Hormônio Paratireóideo/sangue , Período Pré-Operatório , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Sensibilidade e Especificidade , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Fatores de Tempo , Ultrassonografia
15.
World J Clin Cases ; 8(7): 1278-1286, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32337203

RESUMO

BACKGROUND: Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL) is a rare extra-nodal T-cell lymphoma that has uniformly aggressive features with a poor prognosis. No standardized treatment protocols have been established. Previous experience has demonstrated favorable outcomes with combination chemotherapy followed by autologous hematopoietic stem cell transplant. However, many patients are unable to tolerate the toxicities. Chidamide is a new histone deacetylase inhibitor that has shown preferential efficacy in mature T-cell lymphoma. CASE SUMMARY: We herein present two cases of MEITL who were both intermediate risk according to enteropathy-associated T cell lymphoma prognostic index. Case one was a 61-year-old man. He complained of upper abdominal pain and intermittent black stool for 2 mo. Imaging examination revealed that the intestinal wall was thickened. He received a partial excision of the small intestine. A chidamide-based combination regimen was given postoperatively. Eleven months later, he presented with recurrence in the bilateral lungs. He passed away 15 mo after his diagnosis. Case two was a 35-year-old woman who complained of abdominal distention for 1 mo. Positron emission tomography/computed tomography demonstrated wall thickening of the small intestine and upper sigmoid colon. Colon perforation and septic shock occurred on the fourth day of her admission. She was treated by sigmoid colostomy. Chidamide-based combination therapy was then provided. She was recurrence-free for 6 mo until lesions were found in the bilateral brain and lived for 17 mo since her diagnosis. Compared to historical data, chidamide seems to improve the prognosis of MEITL slightly. CONCLUSION: MEITL is a type of aggressive lymphoma. Chidamide is a new promising approach for the treatment of MEITL.

16.
Mol Imaging Biol ; 22(4): 914-923, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31828718

RESUMO

PURPOSE: Externalization of phosphatidylethanolamine (PE) in dying cells makes the phospholipid an attractive target for apoptosis imaging. However, no ideal PE-targeted positron emission tomography (PET) radiotracer was developed. The goal of the study was to develop a novel PE-targeted radiopharmaceutical to imaging apoptosis. PROCEDURE: In this study, we have radiolabeled PE-binding polypeptide duramycin with fluorine-18 for PET imaging of apoptosis. Al[18F]F-NOTA-PEG3-duramycin was synthesized via chelation reaction of NOTA-PEG3-duramycin with Al[18F]F. PE-binding capacity of Al[18F]F-NOTA-PEG3-duramycin was determined in a competitive radiometric PE-binding assay. The pharmacokinetic profile was evaluated in Kunming mice. The apoptosis imaging capacity of Al[18F]F-NOTA-PEG3-duramycin was evaluated using in vitro cell uptake assay with camptothecin-treated Jurkat cells, along with in vivo PET imaging using erlotinib-treated nude mice. RESULTS: The total synthesis procedure lasted for 30 min, with a decay-uncorrected radiochemical yield of 21.3 ± 2.6 % (n = 10). Compared with the control cells, the binding of Al[18F]F-NOTA-PEG3-duramycin with camptothecin-induced apoptotic cells resulted in a tripling increase. A competitive radiometric PE-binding assay strongly confirmed the binding of Al[18F]F-NOTA-PEG3-duramycin to PE. The biodistribution study showed rapid blood clearance, prominent kidney retention, and low liver uptake. In the in vivo PET/CT imaging, Al[18F]F-NOTA-PEG3-duramycin demonstrated 2-fold increase in erlotinib-treated HCC827 tumors in nude mice. CONCLUSION: Considering the facile preparation and improved biological properties, Al[18F]F-NOTA-PEG3-duramycin seems to be a promising PET tracer candidate for imaging apoptosis in the monitoring of cancer treatment.


Assuntos
Apoptose , Radioisótopos de Flúor/química , Sondas Moleculares/química , Fosfatidiletanolaminas/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Bibliotecas de Moléculas Pequenas/química , Coloração e Rotulagem , Animais , Bacteriocinas/farmacologia , Camptotecina/farmacologia , Linhagem Celular Tumoral , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Compostos Organometálicos/química , Peptídeos/farmacologia , Distribuição Tecidual
17.
Phys Chem Chem Phys ; 21(31): 17047-17053, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31360967

RESUMO

Quadrivalent Cr4+ theoretically exhibits great potential to achieve higher photo-luminescence (PL) lifetime based temperature sensitivity than the commonly utilized trivalent Cr3+, but the problem is how to stabilize the anomalous quadrivalent chemical state of Cr4+. Here we propose a type of glass-ceramic phase structure with a precipitated ZnAl2O4 crystalline sub-phase and a residual ZnO-SrO-SiO2 glassy sub-phase, where Cr4+ can be well stabilized in the residual glassy sub-phase. From PL spectra, Cr4+ or Cr3+ was found to be located at Td (tetrahedral crystal filed) or Oh (octahedral crystal filed) sites with a relatively high crystal field strength. The thermally coupled 1E(1D)/3T2(3F) states of Cr4+ or the 2E(2G)/4T2(4F) states of Cr3+ were revealed as competitive energy level pairs suitable for PL lifetime based temperature sensing. Quadrivalent Cr4+ had a particular PL lifetime ratio of 1E(1D)/3T2(3F) up to 103, which was much higher than that (101) of trivalent Cr3+:2E(2G)/4T2(4F). This supported Cr4+ to eventually achieve a higher temperature sensitivity (1.72% K-1) one order of magnitude higher than that of Cr3+ (0.83% K-1). This provides the possibility of utilizing Cr4+-doped glass to develop a type of temperature sensor with high precision and sensitivity.

18.
Phys Chem Chem Phys ; 21(31): 16905-16909, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31099365

RESUMO

The widespread application of hydrocarbon polymers has spurred an increasing interest in the study of their degradation mechanism. In general, the chemical inertness of polymers makes their degradation by low-energy processes a challenging problem. Herein, we report a method of spatial isomerization to make polymers degrade easily. The first-principles calculations show that the energy barrier required for degradation reaction is directly related to the spatial arrangement of the polymer, with the isotactic structure and most atactic structures being easier to degrade than the syndiotactic structure. Therefore, a new way to accelerate the degradation by achieving spatial isomerization of polymers has been proposed. Furthermore, the synthesis rates of these structures have also been calculated to support future experiments.

19.
Theranostics ; 9(4): 1144-1153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30867821

RESUMO

Although 11C-labelled sulfur-containing amino acids (SAAs) including L-methyl-[11C]methionine and S-[11C]-methyl-L-cysteine, are attractive tracers for glioma positron emission tomography (PET) imaging, their applications are limited by the short half-life of the radionuclide 11C (t1/2 = 20.4 min). However, development of 18F-labelled SAAs (18F, t1/2 = 109.8 min) without significant structural changes or relying on prosthetic groups remains to be a great challenge due to the absence of adequate space for chemical modification. Methods: We herein present 18F-trifluoromethylated D- and L-cysteines which were designed by replacing the methyl group with 18F-trifluoromethyl group using a structure-based bioisosterism strategy. These two enantiomers were synthesized stereoselectively from serine-derived cyclic sulfamidates via a nucleophilic 18F-trifluoromethylthiolation reaction followed by a deprotection reaction. Furthermore, we conducted preliminary in vitro and in vivo studies to investigate the feasibility of using 18F-trifluoromethylated cysteines as PET tracers for glioma imaging. Results: The two-step radiosynthesis provided the desired products in excellent enantiopurity (ee > 99%) with 14% ± 3% of radiochemical yield. In vitro cell study demonstrated that both enantiomers were taken up efficiently by C6 tumor cells and were mainly transported by systems L and ASC. Among them, the D-enantiomer exhibited relatively good stability and high tumor-specific accumulation in the animal studies. Conclusion: Our findings indicate that 18F-trifluoromethylated D-cysteine, a new SAA tracer, may be a potential candidate for glioma imaging. Taken together, our study represents a first step toward developing 18F-trifluoromethylated cysteines as structure-mimetic tracers for PET tumor imaging.


Assuntos
Cisteína/isolamento & purificação , Glioma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Traçadores Radioativos , Animais , Cisteína/administração & dosagem , Cisteína/análogos & derivados , Camundongos , Transplante de Neoplasias , Transplante Heterólogo
20.
Mol Imaging Biol ; 21(6): 1127-1137, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30847820

RESUMO

PURPOSE: 2-[18F]Fluoropropionic acid (RS-[18F]FPA) has shown potential value as a short-chain fatty acid positron emission tomography (PET) tracer for the detection of liver cancer. However, RS-[18F]FPA is a mixture of 2-R-[18F]fluoropropionic acid (R-[18F]FPA) and 2-S-[18F]fluoropropionic acid (S-[18F]FPA). The aim of this study is to validate the feasibility of R-[18F]FPA in preclinical PET imaging of liver cancer and to compare the use of R-[18F]FPA with that of RS-[18F]FPA and S-[18F]FPA. PROCEDURES: A comparative study of R-[18F]FPA, RS-[18F]FPA, S-[18F]FPA, and [18F]FDG micro-PET imaging was performed in HepG2 and SK-Hep-1 tumor-bearing mice. A comparison of R-[18F]FPA uptake with that of S-[18F]FPA by HepG2 and SK-Hep-1 cells was made at different time points. Additionally, in vivo blocking experiments in HepG2 and SK-Hep-1 tumor models were conducted with orlistat and 3-nitropropionic acid (3-NP). In vitro blocking experiments with orlistat or 3-NP were performed with HepG2 and SK-Hep-1 cells. RESULTS: The radioactivity uptake values of R-[18F]FPA were comparable to those of RS-[18F]FPA but were higher than those of S-[18F]FPA and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in HepG2 tumors. The radioactivity uptake values of R-[18F]FPA in large HepG2 tumors were lower than those of [18F]FDG (P < 0.05), while R-[18F]FPA PET was significantly superior to [18F]FDG PET in detecting small tumors (both SK-Hep-1 and HepG2 tumors). The in vivo PET imaging experiments showed that R-[18F]FPA uptake in HepG2 tumor-bearing mice was blocked by 19.3 % and 31.8 % after treatment with orlistat and 3-NP, respectively. The radioactivity uptake values of R-[18F]FPA in SK-Hep-1 tumor-bearing mice was blocked by 39.5 % with orlistat. CONCLUSION: R-[18F]FPA seems to be more potential than S-[18F]FPA as an optically pure PET probe, with effective compensation for the deficiencies of [18F]FDG, particularly in PET imaging of small liver cancer. The uptake mechanism of [18F]FPA in liver cancer may be related to fatty acid synthesis and the tricarboxylic acid cycle. However, compared with the racemic RS-[18F]FPA, the possible advantages of R-enantiomer R-[18F]FPA still needs further research.


Assuntos
Fluorocarbonos/química , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/química , Animais , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico , Ácido Graxo Sintases/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Distribuição Tecidual , Tomografia Computadorizada por Raios X
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