Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modi...Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modified with hydrazide, and the attachment of multiple chelated Gd（III） ions to the interior of the nano-suitcases affords nanoscale MRI contrast agents with high relaxivity values. The highly fenestrated dextran shell of the nano-suitcases assures water exchange which readily occurs between the surrounding environment and the Gd（III） ions encapsulated within the hybrid nano-suitcases. The complexation between the hydrophilic hydrazide interior of the nano-suitcases and Gd（III） ions results in an impressive Gd payload at 22.6 wt% in the hybrid nano-suitcases. The longitudinal relaxivity （rl） of the hybrid nano-suitcases is reported as 44.4 L/（mmol-s）, which is 9-14 folds of that of commercial Gd-DTPA agents. In vivo MRI studies demonstrate that the hybrid nano-suitcases accumulated in the lymph node of the rat due to their nanoscale dimensions and displayed strong signals in vivo. The results indicated that the hybrid nano-suitcases provide a promising platform for the diagnosis of lymph node related diseases.展开更多
Mn-TCPP-CSn（n=6,1 1,20） as a type of potential magnetic resonance imaging（MRI） contrast agents were synthesized via manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin（Mn-TCPP） modified with chitosan oligosa...Mn-TCPP-CSn（n=6,1 1,20） as a type of potential magnetic resonance imaging（MRI） contrast agents were synthesized via manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin（Mn-TCPP） modified with chitosan oligosaccharides（CSn）.Experimental data of infared（IR）,UV-Vis,MS,inductively coupled plasma-atomic emission spectrometer（ICP-AES） and size exclusion chromatography evidenced the formation of Mn-TCPP-CSn-The stability results show that Mn-TCPP-CSn in aqueous solution was stable enough to prevent Mn（Ⅱ） ions from leaking.The magnetic properties in vitro indicate that Mn-TCPP-CS20 possesses higher longitudinal relaxivity（r1=10.38 L·mmol^-1·s^-1） in aqueous solution than unmodified porphyrin Mn-TCPPNa4[manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin,tetrasodium salt]（r1=5.10 L·mmol^-1·s^-1） and the commercial contrast agent Gd-DTPA（r1=4.05 L·mmol^-1·s^-1）.The preliminary T1-weighted flash image studies in vitro show that the contrast and the imaging signal of Mn-TCPP-CSn were superior to those of Mn-TCPPNa4 and Gd-DTPA under the same conditions.The 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assay shows that Mn-TCPP-CSn has a good biocompatibility.In addition,the thermodynamical parameters（ΔH〈0,ΔS〈0,ΔG〈0） of Mn-TCPP-CSn bound to bovine serum albumin（BSA） show that Mn-TCPP-CSn could bind to BSA spontaneously,where the binding complex was stabilized mainly by van der Waals interactions and hydrogen bonds.These results suggest that Mn-TCPP-CSn have the advantage of becoming a potential MRI contrast agent.展开更多
Nitroreductases(NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide(NADH) as an electron donor. NTRs are present in a wide range of bacteri...Nitroreductases(NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide(NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T_1-weighted magnetic resonance imaging(MRI)contrast agent Gd-DOTA-PNB(probe 1) has been designed and explored for the possible detection of NTR.Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections.展开更多
Two gadolinium polyoxometalates, KCs4[Gd（a-SiW11O39）].25HzO（POM-1） and K13[Gd（f12-SiWllO39）a]·27H2O（POM-2）, have been evaluated as the candidates of potential magnetic resonance imaging Tl（longitudinal r...Two gadolinium polyoxometalates, KCs4[Gd（a-SiW11O39）].25HzO（POM-1） and K13[Gd（f12-SiWllO39）a]·27H2O（POM-2）, have been evaluated as the candidates of potential magnetic resonance imaging Tl（longitudinal relaxation） contrast agents. Longitudinal relaxivities of POM-2 are much higher than those of POM-1 in pure water and protein solution, respectively. However, compared with POM-1, POM-2 interacts with protein more strongly through electrostatic interaction, which is comfirmed by the fluoresence quenching of human serum albumin（HSA） in solu- tions with different polyoxometalate concentrations. Meanwhile, POM-1 presentes much lower cytotoxicity in the cell viability tests.展开更多
Six new aminocarboxylic ligands were synthesized by reactions of EDTA (ethylenediaminetetraacetic acid) dianhydride or DTPA (dlethylenetriaminepenta-acetic acid) dianhydride and ethyl ester of serine,threonine and tyr...Six new aminocarboxylic ligands were synthesized by reactions of EDTA (ethylenediaminetetraacetic acid) dianhydride or DTPA (dlethylenetriaminepenta-acetic acid) dianhydride and ethyl ester of serine,threonine and tyrosine. Their paramagnetic metal complexes were also synthesized.All ligands and paramagnetic metal complexes were characterized by IR spectra,IH NMR and elemental analyses.Relaxivity study showed that the metal complexes had higher relaxation effectiveness as compared to corresponding unmodified metal complexes. Imaging study of gadolinium complex of tyrosine ethyl ester modified DTPA in mice demonstrated that this metal complex could apparently increase the signal intensity of MR images.展开更多
Liver cancer is the common malignant tumor in China and current treatment is based on surgery. However, liver function of many liver cancer patients is impaired before surgery, so there’s a high possibility of occurr...Liver cancer is the common malignant tumor in China and current treatment is based on surgery. However, liver function of many liver cancer patients is impaired before surgery, so there’s a high possibility of occurrence of liver failure after the tumor resection. Therefore, it’s necessary to accurately evaluate liver function before surgery. Currently, clinical methods are mostly limited to assess the function of overall liver. But the application of hepatocyte-specific contrast agent—gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) makes it possible to assess the function of local liver segment accurately. This paper reviewed the progress of using Gd-EOB-DTPA dynamic contrast enhanced magnetic resonance imaging (MRI) to assess liver function preoperatively, such as parameters selection for liver function assessment, clinical factors affecting Gd-EOB-DTPA enhanced MRI and so on.展开更多
Purpose: To optimize contrast to noise ratio (CNR) in magnetic resonance imaging (MRI) of prostate cancer using at 3T. Methods: CNR was expressed as a difference in MR signals of two samples. Amulti-echo spin-echo (ME...Purpose: To optimize contrast to noise ratio (CNR) in magnetic resonance imaging (MRI) of prostate cancer using at 3T. Methods: CNR was expressed as a difference in MR signals of two samples. Amulti-echo spin-echo (MESE) pulse sequence was used. The theoretical value of the maximum CNR was obtained using the derivative of CNR with echo time (TE) as a variable. The T<sub>1</sub> relaxation time was ignored as repetition time (TR) was assumed to be very long (TR >> T<sub>1</sub>). The theoretical calculations were confirmed with in vitro and in vivo experiments. For in vitro experiments we used samples with different T<sub>2</sub> values using various concentrations of super paramagnetic iron oxide (SPIO) and for in vivo experiments we used an animal model of prostate cancer. Results: CNR was maximized by selecting the optimum TE for a multi-echo spin-echo (MESE) pulse sequence based on theoretical predictions. MR images of prostate cancer at 3T were obtained and showed maximum CNR at the predicted TE. Conclusions: It was possible to maximize CNR of prostate tumour by selecting the optimal TE based on simple theoretical calculations. The proposed method can be applied to other pulse sequences and tissues. It can be applied to any MRI system at any magnetic field. However the method requires knowledge of T<sub>2</sub> relaxation times.展开更多
Objective： To prospectively compare the discriminative capacity of dynamic contrast enhanced-magnetic resonance imaging（DCE-MRI） with that of^18F-fluorodeoxyglucose（^18F-FDG） positron emission tomography/computed...Objective： To prospectively compare the discriminative capacity of dynamic contrast enhanced-magnetic resonance imaging（DCE-MRI） with that of^18F-fluorodeoxyglucose（^18F-FDG） positron emission tomography/computed tomography（PET/CT） in the differentiation of malignant and benign solitary pulmonary nodules（SPNs）.Methods： Forty-nine patients with SPNs were included in this prospective study. Thirty-two of the patients had malignant SPNs, while the other 17 had benign SPNs. All these patients underwent DCE-MRI and ^18F-FDG PET/CT examinations. The quantitative MRI pharmacokinetic parameters, including the trans-endothelial transfer constant（K^trans）, redistribution rate constant（Kep）, and fractional volume（Ve）, were calculated using the Extended-Tofts Linear two-compartment model. The ^18F-FDG PET/CT parameter, maximum standardized uptake value（SUV（max））, was also measured. Spearman＇s correlations were calculated between the MRI pharmacokinetic parameters and the SUV（max） of each SPN. These parameters were statistically compared between the malignant and benign nodules. Receiver operating characteristic（ROC） analyses were used to compare the diagnostic capability between the DCE-MRI and ^18F-FDG PET/CT indexes.Results： Positive correlations were found between K^trans and SUV（max）, and between K（ep） and SUV（max）（P〈0.05）.There were significant differences between the malignant and benign nodules in terms of the K^trans, K（ep） and SUV（max） values（P〈0.05）. The areas under the ROC curve（AUC） of K^trans） K（ep） and SUV（max） between the malignant and benign nodules were 0.909, 0.838 and 0.759, respectively. The sensitivity and specificity in differentiating malignant from benign SPNs were 90.6% and 82.4% for K^trans; 87.5% and 76.5% for K（ep）; and 75.0% and 70.6%for SUV（max）, respectively. The sensitivity and specificity of K^trans and K（ep） were higher than those of SUV（max）, but there was no significant difference between them（P〉0.05）.Conclusions： DCE-MRI can be used to differentiate between benign and malignant SPNs and has the advantage of being radiation free.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.21374061,81371703 and 81501571)the Marie Curie International Incoming Fellowship of the EU+2 种基金the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning“Shu Guang”project supported by Shanghai Municipal Education CommissionShanghai Education Development Foundation
文摘Dextran-poly（glycidyl methacrylate） （Dex-PGMA） nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly （GISA） approach. On this basis, the Dex-PGMA nano-suitcases were modified with hydrazide, and the attachment of multiple chelated Gd（III） ions to the interior of the nano-suitcases affords nanoscale MRI contrast agents with high relaxivity values. The highly fenestrated dextran shell of the nano-suitcases assures water exchange which readily occurs between the surrounding environment and the Gd（III） ions encapsulated within the hybrid nano-suitcases. The complexation between the hydrophilic hydrazide interior of the nano-suitcases and Gd（III） ions results in an impressive Gd payload at 22.6 wt% in the hybrid nano-suitcases. The longitudinal relaxivity （rl） of the hybrid nano-suitcases is reported as 44.4 L/（mmol-s）, which is 9-14 folds of that of commercial Gd-DTPA agents. In vivo MRI studies demonstrate that the hybrid nano-suitcases accumulated in the lymph node of the rat due to their nanoscale dimensions and displayed strong signals in vivo. The results indicated that the hybrid nano-suitcases provide a promising platform for the diagnosis of lymph node related diseases.
基金Supported by the National Natural Science Foundation of China（Nos.21261008, 21302071, 21171076）, and the Cooperation Project of Hainan International Science and Technology, China（No.KJHZ2014-05）.
文摘Mn-TCPP-CSn（n=6,1 1,20） as a type of potential magnetic resonance imaging（MRI） contrast agents were synthesized via manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin（Mn-TCPP） modified with chitosan oligosaccharides（CSn）.Experimental data of infared（IR）,UV-Vis,MS,inductively coupled plasma-atomic emission spectrometer（ICP-AES） and size exclusion chromatography evidenced the formation of Mn-TCPP-CSn-The stability results show that Mn-TCPP-CSn in aqueous solution was stable enough to prevent Mn（Ⅱ） ions from leaking.The magnetic properties in vitro indicate that Mn-TCPP-CS20 possesses higher longitudinal relaxivity（r1=10.38 L·mmol^-1·s^-1） in aqueous solution than unmodified porphyrin Mn-TCPPNa4[manganese（Ⅱ） meso-tetra（4-carboxyphenyl） porphyrin,tetrasodium salt]（r1=5.10 L·mmol^-1·s^-1） and the commercial contrast agent Gd-DTPA（r1=4.05 L·mmol^-1·s^-1）.The preliminary T1-weighted flash image studies in vitro show that the contrast and the imaging signal of Mn-TCPP-CSn were superior to those of Mn-TCPPNa4 and Gd-DTPA under the same conditions.The 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assay shows that Mn-TCPP-CSn has a good biocompatibility.In addition,the thermodynamical parameters（ΔH〈0,ΔS〈0,ΔG〈0） of Mn-TCPP-CSn bound to bovine serum albumin（BSA） show that Mn-TCPP-CSn could bind to BSA spontaneously,where the binding complex was stabilized mainly by van der Waals interactions and hydrogen bonds.These results suggest that Mn-TCPP-CSn have the advantage of becoming a potential MRI contrast agent.
基金supported by Sino-German research project GZ 1271,Peking Union Medical College(PUMC)Youth Fund(No.3332016056),the Innovation Project of Shandong Academy of Medical Sciences
文摘Nitroreductases(NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide(NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T_1-weighted magnetic resonance imaging(MRI)contrast agent Gd-DOTA-PNB(probe 1) has been designed and explored for the possible detection of NTR.Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections.
基金the Natural Science Foundation of Jilin Province,China
文摘Two gadolinium polyoxometalates, KCs4[Gd（a-SiW11O39）].25HzO（POM-1） and K13[Gd（f12-SiWllO39）a]·27H2O（POM-2）, have been evaluated as the candidates of potential magnetic resonance imaging Tl（longitudinal relaxation） contrast agents. Longitudinal relaxivities of POM-2 are much higher than those of POM-1 in pure water and protein solution, respectively. However, compared with POM-1, POM-2 interacts with protein more strongly through electrostatic interaction, which is comfirmed by the fluoresence quenching of human serum albumin（HSA） in solu- tions with different polyoxometalate concentrations. Meanwhile, POM-1 presentes much lower cytotoxicity in the cell viability tests.
文摘Six new aminocarboxylic ligands were synthesized by reactions of EDTA (ethylenediaminetetraacetic acid) dianhydride or DTPA (dlethylenetriaminepenta-acetic acid) dianhydride and ethyl ester of serine,threonine and tyrosine. Their paramagnetic metal complexes were also synthesized.All ligands and paramagnetic metal complexes were characterized by IR spectra,IH NMR and elemental analyses.Relaxivity study showed that the metal complexes had higher relaxation effectiveness as compared to corresponding unmodified metal complexes. Imaging study of gadolinium complex of tyrosine ethyl ester modified DTPA in mice demonstrated that this metal complex could apparently increase the signal intensity of MR images.
文摘Liver cancer is the common malignant tumor in China and current treatment is based on surgery. However, liver function of many liver cancer patients is impaired before surgery, so there’s a high possibility of occurrence of liver failure after the tumor resection. Therefore, it’s necessary to accurately evaluate liver function before surgery. Currently, clinical methods are mostly limited to assess the function of overall liver. But the application of hepatocyte-specific contrast agent—gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) makes it possible to assess the function of local liver segment accurately. This paper reviewed the progress of using Gd-EOB-DTPA dynamic contrast enhanced magnetic resonance imaging (MRI) to assess liver function preoperatively, such as parameters selection for liver function assessment, clinical factors affecting Gd-EOB-DTPA enhanced MRI and so on.
文摘Purpose: To optimize contrast to noise ratio (CNR) in magnetic resonance imaging (MRI) of prostate cancer using at 3T. Methods: CNR was expressed as a difference in MR signals of two samples. Amulti-echo spin-echo (MESE) pulse sequence was used. The theoretical value of the maximum CNR was obtained using the derivative of CNR with echo time (TE) as a variable. The T<sub>1</sub> relaxation time was ignored as repetition time (TR) was assumed to be very long (TR >> T<sub>1</sub>). The theoretical calculations were confirmed with in vitro and in vivo experiments. For in vitro experiments we used samples with different T<sub>2</sub> values using various concentrations of super paramagnetic iron oxide (SPIO) and for in vivo experiments we used an animal model of prostate cancer. Results: CNR was maximized by selecting the optimum TE for a multi-echo spin-echo (MESE) pulse sequence based on theoretical predictions. MR images of prostate cancer at 3T were obtained and showed maximum CNR at the predicted TE. Conclusions: It was possible to maximize CNR of prostate tumour by selecting the optimal TE based on simple theoretical calculations. The proposed method can be applied to other pulse sequences and tissues. It can be applied to any MRI system at any magnetic field. However the method requires knowledge of T<sub>2</sub> relaxation times.
基金supported by the Jiangsu Province Natural Science Foundation (No. BK20161291)the Nantong Science Foundation of China (No. MS2201507)the Nantong Municipal Commission of Health and Family Planning Young Fund (No. WQ2014047)
文摘Objective： To prospectively compare the discriminative capacity of dynamic contrast enhanced-magnetic resonance imaging（DCE-MRI） with that of^18F-fluorodeoxyglucose（^18F-FDG） positron emission tomography/computed tomography（PET/CT） in the differentiation of malignant and benign solitary pulmonary nodules（SPNs）.Methods： Forty-nine patients with SPNs were included in this prospective study. Thirty-two of the patients had malignant SPNs, while the other 17 had benign SPNs. All these patients underwent DCE-MRI and ^18F-FDG PET/CT examinations. The quantitative MRI pharmacokinetic parameters, including the trans-endothelial transfer constant（K^trans）, redistribution rate constant（Kep）, and fractional volume（Ve）, were calculated using the Extended-Tofts Linear two-compartment model. The ^18F-FDG PET/CT parameter, maximum standardized uptake value（SUV（max））, was also measured. Spearman＇s correlations were calculated between the MRI pharmacokinetic parameters and the SUV（max） of each SPN. These parameters were statistically compared between the malignant and benign nodules. Receiver operating characteristic（ROC） analyses were used to compare the diagnostic capability between the DCE-MRI and ^18F-FDG PET/CT indexes.Results： Positive correlations were found between K^trans and SUV（max）, and between K（ep） and SUV（max）（P〈0.05）.There were significant differences between the malignant and benign nodules in terms of the K^trans, K（ep） and SUV（max） values（P〈0.05）. The areas under the ROC curve（AUC） of K^trans） K（ep） and SUV（max） between the malignant and benign nodules were 0.909, 0.838 and 0.759, respectively. The sensitivity and specificity in differentiating malignant from benign SPNs were 90.6% and 82.4% for K^trans; 87.5% and 76.5% for K（ep）; and 75.0% and 70.6%for SUV（max）, respectively. The sensitivity and specificity of K^trans and K（ep） were higher than those of SUV（max）, but there was no significant difference between them（P〉0.05）.Conclusions： DCE-MRI can be used to differentiate between benign and malignant SPNs and has the advantage of being radiation free.
