Objective To evaluate the acute toxicity of 2-deoxy-D-glucose （2DG） by oral （p.o.） and intravenous （i.v.） routes, and also the cardio-respiratory effects following high doses of 2DG in animal models. Methods The...Objective To evaluate the acute toxicity of 2-deoxy-D-glucose （2DG） by oral （p.o.） and intravenous （i.v.） routes, and also the cardio-respiratory effects following high doses of 2DG in animal models. Methods The LD50 of 2DG （in water） was determined in rats and mice by p.o. route and in mice by i.v. route. The effect of 2-DG （250 mg/kg, 500 mg/kg, and 1000 mg/kg, i.v.） was studied on various cardio-respiratory parameters viz., mean arterial blood pressure, heart rate and respiratory rate in anaesthetised rats. The effect of 2DG （500 mg/kg, 1000 mg/kg, and 2000 mg/kg, p.o.） was also studied on various respiratory parameters viz., respiratory rate and tidal volume in conscious rats and mice using a computer program. Results The p.o. LD50 of 2DG was found to be 〉8000 mg/kg in mice and rats, and at this dose no death was observed. The LD50 in mice by i.v. route was found to be 8000 mg/kg. At this dose 2 out of 4 mice died and the death occurred within 6 h. A significant increase in the body weight was observed after p.o. administration of 2DG in rats at 500 mg/kg, 1000 mg/kg, and 2000 mg/kg doses. There was no significant change in the body weight at 4000 mg/kg and 8000 mg/kg by the p.o. route in rats and up to 8000 mg/kg by p.o. as well as i.v. routes in mice. Intravenous administration of 2DG （250 mg/kg, 500 mg/kg, and 1000 mg/kg） in anaesthetised rats showed a time-dependent decrease in the mean arterial blood pressure. There was no change in the heart rate in any of the treatment groups. The tidal volume was not changed significantly by p.o administration in conscious rats, but a significant decrease in the respiratory frequency at 500 mg/kg and 1000 mg/kg doses was observed. In the mice also there was no change in the tidal volume after p.o, administration, but the respiratory frequency decreased significantly at 2000 mg/kg dose. Conclusion 2DG is a safe compound but can cause a fall in the blood pressure and a decrease in respiratory frequency at high doses.展开更多
Beneficial effects of dietary energy restriction (DER), including extension of life-span, reduction in cancer risk, anti-cancer effects and decrease in age related neurodegenerative diseases have been well established...Beneficial effects of dietary energy restriction (DER), including extension of life-span, reduction in cancer risk, anti-cancer effects and decrease in age related neurodegenerative diseases have been well established. Given that DER is difficult to implement in humans due to practical constraints, development of energy restriction mimetics (ERMs) is considered as a suitable alternative. Our recent studies have established the anti-tumor effects of the dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose, a potential ERM, an alternative to DER;without any adverse effects on general physiology. Since functioning of the brain is critically dependent on glucose, we investigated the effects of chronic dietary 2-DG administration on the behavioural outcome in mice. Our findings based on a battery of neuro-behavioural tests clearly suggest that the chronic dietary administration of 2-DG that appreciably impairs the process of tumorigenesis has no adverse effect on the cognitive, affective and sensory-motor functions. Together with the maintenance of normal physiology reported by us earlier, these observations strengthen the potential of dietary 2-DG as a safe cancer preventive strategy.展开更多
Acetylated N-xyloside of 1-naphthylamine(K8A)has been shown to be more potent than 2-deoxy-D-glucose in lung cancer cells and has therapeutic potential for further drug development.In this paper we evaluate and report...Acetylated N-xyloside of 1-naphthylamine(K8A)has been shown to be more potent than 2-deoxy-D-glucose in lung cancer cells and has therapeutic potential for further drug development.In this paper we evaluate and report cytotoxicity,pharmacokinetic,physicochemical and medicinal properties of this D-Xylose derivative(K8A)as a lead anticancer agent with greater therapeutic potential than 2-deoxy-D-glucose(2-DG).2-DG has been in clinical trials for treatment of solid tumors and other types of cancer.We demonstrate using virtual tools that K8A has better“drug-likeness”than 2-DG and does not violate any Lipinski,Ghose,Veber,Egan or Muegge rules.On the other hand,2-DG violates Ghose and Muegge rules.A“BOILEDegg evaluation”,predicts that K8A has higher gastrointestinal absorption(HIA)than 2-DG and is not effluxed by P-glycoprotein(P-gp).Additionally,K8A does not penetrate the blood brain barrier(BBB)and is not a substrate of most Cytochrome P450(CYP)enzymes.Importantly,K8A did not show false positive alert from PAINS screening enabling us to narrow down and rule out false targets.Importantly,K8A is more potent than 2-DG in H1299 and A549 lung cancer cells.展开更多
Background： The detection of solitary pulmonary nodules （SPNs） that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed t...Background： The detection of solitary pulmonary nodules （SPNs） that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography （CT） imaging results remains a significant challenge. The 2-[^18F]-fluoro-2-deoxy-D-glucose （^18F-FDG） positron emission tomography （PET）/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[^18F]-fluorothymidine （^18F-FLT） in lung cancer PET/CT imaging. Methods： The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established （n = 12）, and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values （SUVs）, and Ki-67 proliferation marker expression were investigated. Results： The cell-tracer binding ratio for the A549 cells using the ^18F-FDG was greater than the ratio using 18F-FLT （P 〈 0.05）. The Ki-67 expression showed a significant positive correlation with the ^18F-FLT binding ratio （r = 0.824, P〈 0.01）. The tumor-to-nontumor uptake ratio of ^18F-FDG imaging in xenografts was higher than that of ^18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of ^18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of ^18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of ^18F-FDG and ^18F-FLT （r = 0.658, P〈 0.05 and r = 0.724, P〈 0.01, respectively）. Conclusions： The ^18F-FDG uptake ratio is higher than that of ^18F-FLT in A549 cells at the cellular level.^18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.展开更多
Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the r...Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of <sup>18</sup>F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers.展开更多
The reaction of perfluoroalkyl iodide or perfluoroalkyl bromide with sulfite radical anion (SO_3^-)generated from sodium bisulfite/potassium ferricyanide in water/DMF at 70—75°C gave the corresponding perfluoroa...The reaction of perfluoroalkyl iodide or perfluoroalkyl bromide with sulfite radical anion (SO_3^-)generated from sodium bisulfite/potassium ferricyanide in water/DMF at 70—75°C gave the corresponding perfluoroalkanesulfinate ia good yield.Furthermore,it was shown that the reagent system can also initiate the addition of perfluoroalkyl iodide to olefins or alkynes at 50—65℃.展开更多
A wide variety of surgical related uptake has been reported on F18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography(FDG PET/CT) scan, most of which can be differentiated from neoplastic proces...A wide variety of surgical related uptake has been reported on F18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography(FDG PET/CT) scan, most of which can be differentiated from neoplastic process based on the pattern of FDG uptake and/or anatomic appearance on the integrated CT in image interpretation. A more potential problem we may be aware is postoperative reactive lymphadenitis, which may mimic regional nodal metastases on FDG PET/CT. This review presents five case examples demonstrating that postoperative reactive lymphadenitis could be a false-positive source for regional nodal metastasis on FDG PET/CT. Surgical oncologists and radiologists should be aware of reactive lymphadenitis in interpreting postoperative restaging FDG PET/CT scan when FDG avid lymphadenopathy is only seen in the lymphatic draining location from surgical site.展开更多
Positron emission tomography (PET) imaging has emerged as an important clinical tool for cancer management, and specifically targeted radiopharmaceuticals play critical roles on PET molecular imaging. Solid cancers ha...Positron emission tomography (PET) imaging has emerged as an important clinical tool for cancer management, and specifically targeted radiopharmaceuticals play critical roles on PET molecular imaging. Solid cancers have highly complex and heterogeneous microenvironment, this review focused on those microenvironmental factors such as hypoxia, proliferation and perfusion and, accordingly, a novel test system for validation of current and novel targeted imaging radiopharmaceuticals. In this review, we have introduced the establishment of cancer and metastases models in nude mice, visualization of microenvironmental components of hypoxia, proliferation, perfusion, stroma and necrosis in cancers and metastases for establishing the microenvironment based model system, and validation of several radio- pharmaceuticals such as 18F-fluoro-2-deoxyglucose (18F-FDG) 18F-fluorothymidine (18F-FLT), 18F-misonidazole (18F- FMISO) using the system. We found that 18F-FLT accumulates in proliferating cancer cells, while 18F-FMISO and 18F-FDG mostly accumulate in hypoxic and non-proliferative cancer cells, 18F-FDG shares roughly similar intratumoral distribution pattern with 18F-FMISO and IAZGP, but mutually excludes 18F-FLT. This model system validated current tracers for imaging glucose metabolism, hypoxia and proliferation in cancer and metastases, therefore, can be used for novel targeted radiopharmaceuticals validation.展开更多
Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained wi...Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.展开更多
Objective：To evaluate the clinical value with positron emission tomography/computerized tomography（PET/CT） imaging for the detection of vulnerable plaque in atherosclerotic lesions. Methods：Sixty people with a age...Objective：To evaluate the clinical value with positron emission tomography/computerized tomography（PET/CT） imaging for the detection of vulnerable plaque in atherosclerotic lesions. Methods：Sixty people with a age of over 60[mean age （69.2 ± 7.1）years] underwent three dimension（3D） whole-body fluorine-18-2-fluoro-2-deoxy-D-glucose（^18F-FDG） PET/CT imaging and were evaluated retrospectively, including 6 cases assessed as normal and 54 cases with active atherosclerotic plaque. Fifty-four cases with SUVs and CT values in the aortic wall of high-FDG-uptake were measured retrospectively. These high-FDG-uptake cases in the aortic wall were divided into three groups according their CT value. Cases in group 1 had high uptake in atherosclerotic lesions of the aortic wall with CT value of less than 60 Hu（soft plaque）. Cases in group 2 had high uptake with CT value between 60-100 Hu （intermediate plaque）, Cases in group 3 had high uptake with CT value more than 100 Hu（calcified plaque）, Group 4 was normal. Results： In group 1, there were 42 high-FDG-uptake sites （average SUV 1.553 ± 0.486）. In group 2, there were 30 high-FDG-uptake sites（average SUV 1.393 ± 0.296）. In group 3, there were 36 high-FDG-uptake sites（average SUV 1.354 ± 0.189）. In group 4, there were 33 normal-FDG-uptake sites （average SUV was 1.102 ± 0.141）, The SUVs showed significant difference among the four groups（F = 678.909, P = 0.000）. There were also significant difference found between the normal-FDG-uptake group and the high-FDG-uptake groups（P = 0.000, 0.000, 0.001, respectively）. Conclusion：Different degrees of ^18F-FDG uptake in active large atherosclerotic plaque were shown in different stages of atherosclerotic plaque formation. The soft plaque had the highest FDG uptake in this study. This suggested that ^18F- FDG PET/CT imaging may be of great potential value in early diagnosis and monitoring of vulnerable soft plaque in atherosclerotic lesions.展开更多
Malignant triton tumor (MTT) is a rare variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyosarcomatous differentiation. We report the case of a 54-year-old male without a history of neurofibromato...Malignant triton tumor (MTT) is a rare variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyosarcomatous differentiation. We report the case of a 54-year-old male without a history of neurofibromatosis type 1 (NF1) who had a growing abdominal wall tumor diagnosed as MTT. Computed tomography (CT), magnetic resonance imaging (MRI) and 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography/CT (FDG-PET/CT) were performed. The MRI and FDG-PET/CT indicated that the lateral component of the tumor was composed of many proliferative cells, corresponding to the histopathological finding of a cellular proliferation of spindle-shaped cells. In light of this case and previous reports, it is apparent that FDG-PET/CT is a helpful tool for distinguishing MTT from benign peripheral nerve sheath tumor.展开更多
文摘Objective To evaluate the acute toxicity of 2-deoxy-D-glucose （2DG） by oral （p.o.） and intravenous （i.v.） routes, and also the cardio-respiratory effects following high doses of 2DG in animal models. Methods The LD50 of 2DG （in water） was determined in rats and mice by p.o. route and in mice by i.v. route. The effect of 2-DG （250 mg/kg, 500 mg/kg, and 1000 mg/kg, i.v.） was studied on various cardio-respiratory parameters viz., mean arterial blood pressure, heart rate and respiratory rate in anaesthetised rats. The effect of 2DG （500 mg/kg, 1000 mg/kg, and 2000 mg/kg, p.o.） was also studied on various respiratory parameters viz., respiratory rate and tidal volume in conscious rats and mice using a computer program. Results The p.o. LD50 of 2DG was found to be 〉8000 mg/kg in mice and rats, and at this dose no death was observed. The LD50 in mice by i.v. route was found to be 8000 mg/kg. At this dose 2 out of 4 mice died and the death occurred within 6 h. A significant increase in the body weight was observed after p.o. administration of 2DG in rats at 500 mg/kg, 1000 mg/kg, and 2000 mg/kg doses. There was no significant change in the body weight at 4000 mg/kg and 8000 mg/kg by the p.o. route in rats and up to 8000 mg/kg by p.o. as well as i.v. routes in mice. Intravenous administration of 2DG （250 mg/kg, 500 mg/kg, and 1000 mg/kg） in anaesthetised rats showed a time-dependent decrease in the mean arterial blood pressure. There was no change in the heart rate in any of the treatment groups. The tidal volume was not changed significantly by p.o administration in conscious rats, but a significant decrease in the respiratory frequency at 500 mg/kg and 1000 mg/kg doses was observed. In the mice also there was no change in the tidal volume after p.o, administration, but the respiratory frequency decreased significantly at 2000 mg/kg dose. Conclusion 2DG is a safe compound but can cause a fall in the blood pressure and a decrease in respiratory frequency at high doses.
文摘Beneficial effects of dietary energy restriction (DER), including extension of life-span, reduction in cancer risk, anti-cancer effects and decrease in age related neurodegenerative diseases have been well established. Given that DER is difficult to implement in humans due to practical constraints, development of energy restriction mimetics (ERMs) is considered as a suitable alternative. Our recent studies have established the anti-tumor effects of the dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose, a potential ERM, an alternative to DER;without any adverse effects on general physiology. Since functioning of the brain is critically dependent on glucose, we investigated the effects of chronic dietary 2-DG administration on the behavioural outcome in mice. Our findings based on a battery of neuro-behavioural tests clearly suggest that the chronic dietary administration of 2-DG that appreciably impairs the process of tumorigenesis has no adverse effect on the cognitive, affective and sensory-motor functions. Together with the maintenance of normal physiology reported by us earlier, these observations strengthen the potential of dietary 2-DG as a safe cancer preventive strategy.
文摘Acetylated N-xyloside of 1-naphthylamine(K8A)has been shown to be more potent than 2-deoxy-D-glucose in lung cancer cells and has therapeutic potential for further drug development.In this paper we evaluate and report cytotoxicity,pharmacokinetic,physicochemical and medicinal properties of this D-Xylose derivative(K8A)as a lead anticancer agent with greater therapeutic potential than 2-deoxy-D-glucose(2-DG).2-DG has been in clinical trials for treatment of solid tumors and other types of cancer.We demonstrate using virtual tools that K8A has better“drug-likeness”than 2-DG and does not violate any Lipinski,Ghose,Veber,Egan or Muegge rules.On the other hand,2-DG violates Ghose and Muegge rules.A“BOILEDegg evaluation”,predicts that K8A has higher gastrointestinal absorption(HIA)than 2-DG and is not effluxed by P-glycoprotein(P-gp).Additionally,K8A does not penetrate the blood brain barrier(BBB)and is not a substrate of most Cytochrome P450(CYP)enzymes.Importantly,K8A did not show false positive alert from PAINS screening enabling us to narrow down and rule out false targets.Importantly,K8A is more potent than 2-DG in H1299 and A549 lung cancer cells.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81271607）, and the National Postdoctoral Science Foundation of China （No. 2015M572810）.
文摘Background： The detection of solitary pulmonary nodules （SPNs） that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography （CT） imaging results remains a significant challenge. The 2-[^18F]-fluoro-2-deoxy-D-glucose （^18F-FDG） positron emission tomography （PET）/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[^18F]-fluorothymidine （^18F-FLT） in lung cancer PET/CT imaging. Methods： The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established （n = 12）, and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values （SUVs）, and Ki-67 proliferation marker expression were investigated. Results： The cell-tracer binding ratio for the A549 cells using the ^18F-FDG was greater than the ratio using 18F-FLT （P 〈 0.05）. The Ki-67 expression showed a significant positive correlation with the ^18F-FLT binding ratio （r = 0.824, P〈 0.01）. The tumor-to-nontumor uptake ratio of ^18F-FDG imaging in xenografts was higher than that of ^18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of ^18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of ^18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of ^18F-FDG and ^18F-FLT （r = 0.658, P〈 0.05 and r = 0.724, P〈 0.01, respectively）. Conclusions： The ^18F-FDG uptake ratio is higher than that of ^18F-FLT in A549 cells at the cellular level.^18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs.
文摘Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of <sup>18</sup>F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers.
基金This work was partially supported by the National Natural Science Foundation of China.
文摘The reaction of perfluoroalkyl iodide or perfluoroalkyl bromide with sulfite radical anion (SO_3^-)generated from sodium bisulfite/potassium ferricyanide in water/DMF at 70—75°C gave the corresponding perfluoroalkanesulfinate ia good yield.Furthermore,it was shown that the reagent system can also initiate the addition of perfluoroalkyl iodide to olefins or alkynes at 50—65℃.
文摘A wide variety of surgical related uptake has been reported on F18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography(FDG PET/CT) scan, most of which can be differentiated from neoplastic process based on the pattern of FDG uptake and/or anatomic appearance on the integrated CT in image interpretation. A more potential problem we may be aware is postoperative reactive lymphadenitis, which may mimic regional nodal metastases on FDG PET/CT. This review presents five case examples demonstrating that postoperative reactive lymphadenitis could be a false-positive source for regional nodal metastasis on FDG PET/CT. Surgical oncologists and radiologists should be aware of reactive lymphadenitis in interpreting postoperative restaging FDG PET/CT scan when FDG avid lymphadenopathy is only seen in the lymphatic draining location from surgical site.
文摘Positron emission tomography (PET) imaging has emerged as an important clinical tool for cancer management, and specifically targeted radiopharmaceuticals play critical roles on PET molecular imaging. Solid cancers have highly complex and heterogeneous microenvironment, this review focused on those microenvironmental factors such as hypoxia, proliferation and perfusion and, accordingly, a novel test system for validation of current and novel targeted imaging radiopharmaceuticals. In this review, we have introduced the establishment of cancer and metastases models in nude mice, visualization of microenvironmental components of hypoxia, proliferation, perfusion, stroma and necrosis in cancers and metastases for establishing the microenvironment based model system, and validation of several radio- pharmaceuticals such as 18F-fluoro-2-deoxyglucose (18F-FDG) 18F-fluorothymidine (18F-FLT), 18F-misonidazole (18F- FMISO) using the system. We found that 18F-FLT accumulates in proliferating cancer cells, while 18F-FMISO and 18F-FDG mostly accumulate in hypoxic and non-proliferative cancer cells, 18F-FDG shares roughly similar intratumoral distribution pattern with 18F-FMISO and IAZGP, but mutually excludes 18F-FLT. This model system validated current tracers for imaging glucose metabolism, hypoxia and proliferation in cancer and metastases, therefore, can be used for novel targeted radiopharmaceuticals validation.
文摘Objective:To explore the effect of the protease inhibitor from Agaricus bisporus(J.E.Lange)Imbach(AbPI)on glucose uptake and oxidative stress in 3 T3-L1 adipocytes.Methods:Adipocytes were differentiated and stained with OilRed-O staining to confirm adipogenesis.The toxic/protective effect of AbPI on the adipocytes was determined by MTT assay,intracellular reactive oxygen species generation through flow cytometry,and morphologically through confocal microscopy using propidium iodide,4,6-diamino-2-phenylindol dihydrochloride,and 2’,7’-dichlorofluorescein diacetate dyes.The uptake of fluorescent glucose analog,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose by adipocytes was also studied through confocal microscopy.Results:MTT assay showed that the cell survival rate was(28.00±3.00)%,(92.33±2.60)%,and(71.34±2.10)%in the presence of 2 mM H2O2,AbPI alone,and AbPI and H2O2 both,respectively,in comparison to the control.Oil-Red-O staining indicated that Ab PI enhanced adipogenesis.AbPI stimulated the glucose uptake by adipocytes similar to the drug rosiglitazone,and showed insulinsensitizing effect in the presence of insulin,but failed to stimulate the uptake in the absence of insulin.Intracellular reactive oxygen species generation was reduced in differentiating adipocytes upon Ab PI treatment.Confocal microscopy showed that the damaged cell population rose to 3.50%,117.84%,and 261.50%in the presence of Ab PI alone,AbPI with H2O2,and H2O2 alone,respectively.Conclusions:The protease inhibitor enhances glucose uptake by adipocytes and exhibits a cytoprotective effect on them.
文摘Objective：To evaluate the clinical value with positron emission tomography/computerized tomography（PET/CT） imaging for the detection of vulnerable plaque in atherosclerotic lesions. Methods：Sixty people with a age of over 60[mean age （69.2 ± 7.1）years] underwent three dimension（3D） whole-body fluorine-18-2-fluoro-2-deoxy-D-glucose（^18F-FDG） PET/CT imaging and were evaluated retrospectively, including 6 cases assessed as normal and 54 cases with active atherosclerotic plaque. Fifty-four cases with SUVs and CT values in the aortic wall of high-FDG-uptake were measured retrospectively. These high-FDG-uptake cases in the aortic wall were divided into three groups according their CT value. Cases in group 1 had high uptake in atherosclerotic lesions of the aortic wall with CT value of less than 60 Hu（soft plaque）. Cases in group 2 had high uptake with CT value between 60-100 Hu （intermediate plaque）, Cases in group 3 had high uptake with CT value more than 100 Hu（calcified plaque）, Group 4 was normal. Results： In group 1, there were 42 high-FDG-uptake sites （average SUV 1.553 ± 0.486）. In group 2, there were 30 high-FDG-uptake sites（average SUV 1.393 ± 0.296）. In group 3, there were 36 high-FDG-uptake sites（average SUV 1.354 ± 0.189）. In group 4, there were 33 normal-FDG-uptake sites （average SUV was 1.102 ± 0.141）, The SUVs showed significant difference among the four groups（F = 678.909, P = 0.000）. There were also significant difference found between the normal-FDG-uptake group and the high-FDG-uptake groups（P = 0.000, 0.000, 0.001, respectively）. Conclusion：Different degrees of ^18F-FDG uptake in active large atherosclerotic plaque were shown in different stages of atherosclerotic plaque formation. The soft plaque had the highest FDG uptake in this study. This suggested that ^18F- FDG PET/CT imaging may be of great potential value in early diagnosis and monitoring of vulnerable soft plaque in atherosclerotic lesions.
文摘Malignant triton tumor (MTT) is a rare variant of malignant peripheral nerve sheath tumor (MPNST) with rhabdomyosarcomatous differentiation. We report the case of a 54-year-old male without a history of neurofibromatosis type 1 (NF1) who had a growing abdominal wall tumor diagnosed as MTT. Computed tomography (CT), magnetic resonance imaging (MRI) and 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography/CT (FDG-PET/CT) were performed. The MRI and FDG-PET/CT indicated that the lateral component of the tumor was composed of many proliferative cells, corresponding to the histopathological finding of a cellular proliferation of spindle-shaped cells. In light of this case and previous reports, it is apparent that FDG-PET/CT is a helpful tool for distinguishing MTT from benign peripheral nerve sheath tumor.
