Hepatocellular carcinoma(HCC)is one of the leading causes of cancer mortality worldwide.Various imaging modalities provide important information about HCC for its clinical management.Since positron-emission tomography...Hepatocellular carcinoma(HCC)is one of the leading causes of cancer mortality worldwide.Various imaging modalities provide important information about HCC for its clinical management.Since positron-emission tomography(PET)or PET-computed tomography was introduced to the oncologic setting,it has played crucial roles in detecting,distinguishing,accurately staging,and evaluating local,residual,and recurrent HCC.PET imaging visualizes tissue metabolic information that is closely associated with treatment.Dynamic PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC diagnosis.The advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment surveillance.The current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.展开更多
Positron emission tomography （PET） is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes wh...Positron emission tomography （PET） is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including genetically- engineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.展开更多
以[^(14)C]碳酸钡为放射性同位素原料,通过格氏反应、Curtius重排、亲核加成、硫代及关环等7步反应,制备了同位素碳-14标记的毒氟磷粗品,经反相高效液相色谱(RP-HPLC)纯化获得标记物纯品^(14)C-毒氟磷(N-[2-(4-甲基苯并[2-^(14)C]噻唑基...以[^(14)C]碳酸钡为放射性同位素原料,通过格氏反应、Curtius重排、亲核加成、硫代及关环等7步反应,制备了同位素碳-14标记的毒氟磷粗品,经反相高效液相色谱(RP-HPLC)纯化获得标记物纯品^(14)C-毒氟磷(N-[2-(4-甲基苯并[2-^(14)C]噻唑基)]-2-氨基-2-氟代苯基-O,O-二乙基甲基膦酸酯,38.3 m Ci)。7步反应的化学收率/放化收率为10%。其结构经核磁共振氢谱、质谱和放射性高效液相色谱(HPLC-FSA)分析确认。放射性薄层成像分析(TLC-IIA)、高效液相色谱-液体闪烁测量联用分析(HPLC-LSC)、高效液相色谱-流动液体闪烁测量/二极管阵列检测器/质谱联用分析(HPLC-FSA/PDA/MS)和LSC分析表明,^(14)C-毒氟磷的放化纯度和化学纯度均大于98%,比活度为58.0 m Ci/mmol,可作为放射性示踪剂,用于毒氟磷的代谢和环境行为等研究。展开更多
With the rapid development of nanosciences and nanotechnology, a wide variety of manufactured nanomaterials are now used in commodities, pharmaceutics, cosmetics, biomedical products, and industries. While nanomateria...With the rapid development of nanosciences and nanotechnology, a wide variety of manufactured nanomaterials are now used in commodities, pharmaceutics, cosmetics, biomedical products, and industries. While nanomaterials possess more novel and unique physicochemical properties than bulk materials, they also have an unpredictable impact on human health. In the pharmacology and toxicology studies of nanomaterials, it is essential to know the basic behavior in vivo, i.e. absorption, distribution, metabolism, and excretion (ADME) of these newly designed materials. Radiotracer techniques are especially well suited to such studies and have got the chance to demonstrate their enchantment. In this paper, radiolabeling methods for carbon nanomaterials, metallic and metal oxide nanoparticles, etc. are summarized and the applications of the radiolabeled nanomaterials in pharmacology and toxicology studies are outlined.展开更多
以[^(14)C]碳酸钡为放射性同位素原料,通过乙炔环三聚、苯羧基化和甲基化、胺化、环化、亲核取代、格氏、还原、氧化等反应和反相高效液相色谱(HPLC)纯化获得了2种放射性同位素碳-14标记毒氟磷[N-[2-(4-甲基[苯基-U-^(14)C_6]苯并噻唑基...以[^(14)C]碳酸钡为放射性同位素原料,通过乙炔环三聚、苯羧基化和甲基化、胺化、环化、亲核取代、格氏、还原、氧化等反应和反相高效液相色谱(HPLC)纯化获得了2种放射性同位素碳-14标记毒氟磷[N-[2-(4-甲基[苯基-U-^(14)C_6]苯并噻唑基)]-2-氨基-2-氟苯基-O,O-二乙基甲基膦酸酯(2,20.6 m Ci)和N-[2-(4-甲基苯并噻唑基)]-2-氨基-2-氟苯基-O,O-二乙基[^(14)C]甲基膦酸酯(3,32.4 m Ci)],其结构经核磁共振氢谱(~1H NMR)和在线放射性高效液相色谱-二极管阵列检测器/质谱联用(HPLC-FSA/PDA/MS)分析确认,反应总放化收率/化学收率分别为31%和67%.放射性薄层层析-同位素成像分析(TLC-IIA)、离线放射性高效液相色谱(HPLC-LSC),HPLC-FSA/PDA/MS和液体闪烁测量(LSC)分析表明,两种标记物的放化纯度和化学纯度均大于98%,比活度分别为25.5,55.5 m Ci/mmol.该标记物可作为放射性示踪剂,用于毒氟磷的代谢、残留和环境行为等研究.展开更多
Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-pro...Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-promoted difluorocarbene-derived^(19)F/^(18)F-trifluoromethylation of iodotriazoles using KF/K^(18)F as the fluorine source.This approach rapidly generated a wide range of 5-trifluoromethyl-1,2,3-triazoles in good yields showing high functional group compatibility.The reaction was effective for late-stage functionalization of bioactive molecules and^(18)F-trifluoromethylation of iodotriazoles.This work provides a practical synthetic methodology for the development of triazole drugs and^(18)F-radiotracers for positron emission tomography.展开更多
To develop new tumor targeting macromolecular conjugates,poly（HPMA）-SD-APMA-DTPA（HPMA：N-（2-hydroxypropyl）- methacrylamide;APMA：N-（3-ammopropyl）methacrylamide;DTPA：diethylenetriaminepentaacetic acid;SD：sulfa...To develop new tumor targeting macromolecular conjugates,poly（HPMA）-SD-APMA-DTPA（HPMA：N-（2-hydroxypropyl）- methacrylamide;APMA：N-（3-ammopropyl）methacrylamide;DTPA：diethylenetriaminepentaacetic acid;SD：sulfadiazine） was synthesized and characterized.The poly（HPMA）-SD-DTPA conjugates were radiolabeled with the radionuclide ^（99m）Tc and tested for uptake by cultured H22 cells in vitro.DTPA-^（99m）Tc（radiotracer 1） and poly（HPMA）-DTPA-^（99m）Tc（radiotracer 2） were also synthesized and characterized for comparison.The uptake of poly（HPMA）-SD-DTPA-^（99m）Tc（radiotracer 3,34.76%） was significantly higher than that of poly（HPMA）-DTPA-^（99m）Tc（16.40%）,indicating that uptake of the poly（HPMA）-SD-DTPA-^（99m）T was active binding.The uptake of poly（HPMA）-DTPA-^（99m）Tc was significantly higher than that of DTPA-^（99m）Tc（2.98%）, suggesting that uptake of the poly（HPMA）-DTPA-^（99m）T was passive binding.The data suggest that the poly（HPMA）-SDAPMA -DTPA conjugates might be useful as tumor targeting macromolecular conjugates.展开更多
1-[^18F]Fluoro-l-deoxy-2,5-anhydro-D-mannitol （3, ^18F-FDAM） has been synthesized in 6 steps starting from 2,5-anhydro-D-mannitol （2,5-AM） and evaluated as a new radiotracer for PET imaging of MCF-7 breast tumor. ...1-[^18F]Fluoro-l-deoxy-2,5-anhydro-D-mannitol （3, ^18F-FDAM） has been synthesized in 6 steps starting from 2,5-anhydro-D-mannitol （2,5-AM） and evaluated as a new radiotracer for PET imaging of MCF-7 breast tumor. The result of PET imaging study showed that 3 displayed a slightly higher uptake by breast tumor in comparison with the normal breast tissue, implying the possibility of development of PET radiotraeers based on targeting fructose transporters.展开更多
Radiotracer technology has been applied in industry for the investigation of process performance, online monitoring of conditions of process units, troubleshooting and diagnosing anomalies including mixing conditions ...Radiotracer technology has been applied in industry for the investigation of process performance, online monitoring of conditions of process units, troubleshooting and diagnosing anomalies including mixing conditions in continuous stirred tank reactors. In this study, radiotracer methodology was used to carry out investigation on a laboratory water flow rig which serves as simulator of industrial processes. The aims of the investigation were to assess: i) the effect of impeller type on mixing and ii) the fluid dynamics of the water in the vessels since both the vessels and the impellers were redesigned and reconstructed. Four similar vessels in series circuit with different impeller configurations were investigated. Tank 1 has 1 axial impeller, Tank 2 has 2 axial impellers, Tank 3 has 2 radial impellers and Tank 4 has no impeller. The data were collected by introducing 8 mCi liquid technetium-99 m at the inlet stream of the vessels and the gamma signal was detected with thallium activated NaI detector placed at the outlet of the vessels. Residence Time Distribution (RTD) curves for the outlet tracer concentration were generated from which the Mean Residence Time (MRT) and the variance were calculated by the method of moments. The extent of material mixing in the vessels was inferred from the variances and the fluid dynamics was obtained by modeling. The extent of mixing was highest in Tank 2 followed by Tank 3, and Tank 4 gave the poorest mixing. The outlet response curves were fitted with mathematical models using DTS pro and “RTD Software”. The best fit for Tanks 2, 3 and 4 was Perfect Mixers in Series with Exchange (PMSE) model while Perfect Mixers in Series with Recycle (PMSR) model best described the fluid dynamics of the material in Tank 1.展开更多
To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly（HPMA）-APMA-DTPA[HPMA=N-（2-hydroxypropyl） methacrylamide; APMA=N-（3-aminopropyl）methacry...To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly（HPMA）-APMA-DTPA[HPMA=N-（2-hydroxypropyl） methacrylamide; APMA=N-（3-aminopropyl）methacrylamide; DTPA=diethylenetriaminepentaacetic acidl was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N＇-azobis（isobutyronitrile） as the initiator. The copolymers were characterized with nuclear magnetic resonance（NMR） spectroscopy and gel permeation chromatography（GPC, Mn=2.2xl04, Mw/Mn=l.38）. Subsequently, poly（HPMA）-APMA-DTPA was conjugated with 99mTC radionuclide. Prolonged retention of poly（HPMA）-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography（SPECT-CT） at 1, 2, 4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice. DTPA-99mTc was also synthesized and characterized for comparison. The data suggest that the poly（HPMA）-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans.展开更多
基金Supported by the National Natural Science Foundation of China,No.81760306the Basic Research on Application of Joint Special Funding of Science and Technology Department of Yunnan Province-Kunming Medical University,No.2018FE001(-291)
文摘Hepatocellular carcinoma(HCC)is one of the leading causes of cancer mortality worldwide.Various imaging modalities provide important information about HCC for its clinical management.Since positron-emission tomography(PET)or PET-computed tomography was introduced to the oncologic setting,it has played crucial roles in detecting,distinguishing,accurately staging,and evaluating local,residual,and recurrent HCC.PET imaging visualizes tissue metabolic information that is closely associated with treatment.Dynamic PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC diagnosis.The advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment surveillance.The current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.
文摘Positron emission tomography （PET） is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including genetically- engineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.
文摘以[^(14)C]碳酸钡为放射性同位素原料,通过格氏反应、Curtius重排、亲核加成、硫代及关环等7步反应,制备了同位素碳-14标记的毒氟磷粗品,经反相高效液相色谱(RP-HPLC)纯化获得标记物纯品^(14)C-毒氟磷(N-[2-(4-甲基苯并[2-^(14)C]噻唑基)]-2-氨基-2-氟代苯基-O,O-二乙基甲基膦酸酯,38.3 m Ci)。7步反应的化学收率/放化收率为10%。其结构经核磁共振氢谱、质谱和放射性高效液相色谱(HPLC-FSA)分析确认。放射性薄层成像分析(TLC-IIA)、高效液相色谱-液体闪烁测量联用分析(HPLC-LSC)、高效液相色谱-流动液体闪烁测量/二极管阵列检测器/质谱联用分析(HPLC-FSA/PDA/MS)和LSC分析表明,^(14)C-毒氟磷的放化纯度和化学纯度均大于98%,比活度为58.0 m Ci/mmol,可作为放射性示踪剂,用于毒氟磷的代谢和环境行为等研究。
基金Supported by the National Basic Research and Development Program of China (Grant Nos. 2006CB705605 and 2006CB932505)Chinese Academy of Sciences (Grant No. KJCX3.SYW.N3)National Natural Science Foundation of China (Grant Nos. 10525524, 10505024 and 20707027)
文摘With the rapid development of nanosciences and nanotechnology, a wide variety of manufactured nanomaterials are now used in commodities, pharmaceutics, cosmetics, biomedical products, and industries. While nanomaterials possess more novel and unique physicochemical properties than bulk materials, they also have an unpredictable impact on human health. In the pharmacology and toxicology studies of nanomaterials, it is essential to know the basic behavior in vivo, i.e. absorption, distribution, metabolism, and excretion (ADME) of these newly designed materials. Radiotracer techniques are especially well suited to such studies and have got the chance to demonstrate their enchantment. In this paper, radiolabeling methods for carbon nanomaterials, metallic and metal oxide nanoparticles, etc. are summarized and the applications of the radiolabeled nanomaterials in pharmacology and toxicology studies are outlined.
文摘以[^(14)C]碳酸钡为放射性同位素原料,通过乙炔环三聚、苯羧基化和甲基化、胺化、环化、亲核取代、格氏、还原、氧化等反应和反相高效液相色谱(HPLC)纯化获得了2种放射性同位素碳-14标记毒氟磷[N-[2-(4-甲基[苯基-U-^(14)C_6]苯并噻唑基)]-2-氨基-2-氟苯基-O,O-二乙基甲基膦酸酯(2,20.6 m Ci)和N-[2-(4-甲基苯并噻唑基)]-2-氨基-2-氟苯基-O,O-二乙基[^(14)C]甲基膦酸酯(3,32.4 m Ci)],其结构经核磁共振氢谱(~1H NMR)和在线放射性高效液相色谱-二极管阵列检测器/质谱联用(HPLC-FSA/PDA/MS)分析确认,反应总放化收率/化学收率分别为31%和67%.放射性薄层层析-同位素成像分析(TLC-IIA)、离线放射性高效液相色谱(HPLC-LSC),HPLC-FSA/PDA/MS和液体闪烁测量(LSC)分析表明,两种标记物的放化纯度和化学纯度均大于98%,比活度分别为25.5,55.5 m Ci/mmol.该标记物可作为放射性示踪剂,用于毒氟磷的代谢、残留和环境行为等研究.
基金financially supported by the National Natural Science Foundation of China(Nos.21977075,22271200,21801178,21907070,81971653)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,Central Plains Science and Technology Innovation Leader Project(No.214200510008 to L.Li)Scientific and Technological Innovation Team of Colleges and Universities in Henan Province(No.21IRTSTHN001)。
文摘Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-promoted difluorocarbene-derived^(19)F/^(18)F-trifluoromethylation of iodotriazoles using KF/K^(18)F as the fluorine source.This approach rapidly generated a wide range of 5-trifluoromethyl-1,2,3-triazoles in good yields showing high functional group compatibility.The reaction was effective for late-stage functionalization of bioactive molecules and^(18)F-trifluoromethylation of iodotriazoles.This work provides a practical synthetic methodology for the development of triazole drugs and^(18)F-radiotracers for positron emission tomography.
基金the National Natural Science Foundation of China(No.20964003)for funding
文摘To develop new tumor targeting macromolecular conjugates,poly（HPMA）-SD-APMA-DTPA（HPMA：N-（2-hydroxypropyl）- methacrylamide;APMA：N-（3-ammopropyl）methacrylamide;DTPA：diethylenetriaminepentaacetic acid;SD：sulfadiazine） was synthesized and characterized.The poly（HPMA）-SD-DTPA conjugates were radiolabeled with the radionuclide ^（99m）Tc and tested for uptake by cultured H22 cells in vitro.DTPA-^（99m）Tc（radiotracer 1） and poly（HPMA）-DTPA-^（99m）Tc（radiotracer 2） were also synthesized and characterized for comparison.The uptake of poly（HPMA）-SD-DTPA-^（99m）Tc（radiotracer 3,34.76%） was significantly higher than that of poly（HPMA）-DTPA-^（99m）Tc（16.40%）,indicating that uptake of the poly（HPMA）-SD-DTPA-^（99m）T was active binding.The uptake of poly（HPMA）-DTPA-^（99m）Tc was significantly higher than that of DTPA-^（99m）Tc（2.98%）, suggesting that uptake of the poly（HPMA）-DTPA-^（99m）T was passive binding.The data suggest that the poly（HPMA）-SDAPMA -DTPA conjugates might be useful as tumor targeting macromolecular conjugates.
文摘1-[^18F]Fluoro-l-deoxy-2,5-anhydro-D-mannitol （3, ^18F-FDAM） has been synthesized in 6 steps starting from 2,5-anhydro-D-mannitol （2,5-AM） and evaluated as a new radiotracer for PET imaging of MCF-7 breast tumor. The result of PET imaging study showed that 3 displayed a slightly higher uptake by breast tumor in comparison with the normal breast tissue, implying the possibility of development of PET radiotraeers based on targeting fructose transporters.
文摘Radiotracer technology has been applied in industry for the investigation of process performance, online monitoring of conditions of process units, troubleshooting and diagnosing anomalies including mixing conditions in continuous stirred tank reactors. In this study, radiotracer methodology was used to carry out investigation on a laboratory water flow rig which serves as simulator of industrial processes. The aims of the investigation were to assess: i) the effect of impeller type on mixing and ii) the fluid dynamics of the water in the vessels since both the vessels and the impellers were redesigned and reconstructed. Four similar vessels in series circuit with different impeller configurations were investigated. Tank 1 has 1 axial impeller, Tank 2 has 2 axial impellers, Tank 3 has 2 radial impellers and Tank 4 has no impeller. The data were collected by introducing 8 mCi liquid technetium-99 m at the inlet stream of the vessels and the gamma signal was detected with thallium activated NaI detector placed at the outlet of the vessels. Residence Time Distribution (RTD) curves for the outlet tracer concentration were generated from which the Mean Residence Time (MRT) and the variance were calculated by the method of moments. The extent of material mixing in the vessels was inferred from the variances and the fluid dynamics was obtained by modeling. The extent of mixing was highest in Tank 2 followed by Tank 3, and Tank 4 gave the poorest mixing. The outlet response curves were fitted with mathematical models using DTS pro and “RTD Software”. The best fit for Tanks 2, 3 and 4 was Perfect Mixers in Series with Exchange (PMSE) model while Perfect Mixers in Series with Recycle (PMSR) model best described the fluid dynamics of the material in Tank 1.
基金the National Natural Science Foundation of China
文摘To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly（HPMA）-APMA-DTPA[HPMA=N-（2-hydroxypropyl） methacrylamide; APMA=N-（3-aminopropyl）methacrylamide; DTPA=diethylenetriaminepentaacetic acidl was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N＇-azobis（isobutyronitrile） as the initiator. The copolymers were characterized with nuclear magnetic resonance（NMR） spectroscopy and gel permeation chromatography（GPC, Mn=2.2xl04, Mw/Mn=l.38）. Subsequently, poly（HPMA）-APMA-DTPA was conjugated with 99mTC radionuclide. Prolonged retention of poly（HPMA）-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography（SPECT-CT） at 1, 2, 4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice. DTPA-99mTc was also synthesized and characterized for comparison. The data suggest that the poly（HPMA）-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans.
