Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceut...Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceutical research has played an importantrole in multiple disciplines,particularly in translational oncology.Based on the natural phenomenon of necrosis avidity,Onco Ci Dia has emerged as a novel generic approach for treating solid malignancies.Under this systemic dual targeting strategy,a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin(123IHyp),a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation.In this review,by emphasizing the potential clinical applicability of Onco Ci Dia,we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution,dosimetry,pharmacokinetic and,chemical and radiochemical toxicities of the preparations.Myocardial infarction is a global health problem.Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability,searching for diagnostic imaging agents with authentic necrosis avidity is pursued.Therefore,a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated.Cholelithiasis or gallstone disease may cause gallbladder inflammation,infection and other severe complications.While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives,their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones.The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented.Multiple uses of automatic contrast injectors may reduce costs and save resources.However,cross-contaminations with bloodborne pathogens of infectious diseases may occur.We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system.By mimicking pathogens with a radiotracer,we assessed the feasibility of using the system repeatedly without septic risks.This overview is deemed to be interesting to those involvedin the related fields for translational research.展开更多
AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones fr...AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.展开更多
基金Supported by the KU Leuven Molecular Small Animal Imaging Center Mo SAIC(KUL EF/05/08)the center of excellence in vivo molecular imaging research+3 种基金KU Leuven projects IOF-HB/08/009 and IOF-HB/12/018the European Union(AsiaLink Cf P 2006-Europe Aid/123738/C/ACt/Multi-Proposal No.128-498/111)the National Natural Science Foundation of China,No.81071828the Jiangsu Provincial Natural Science Foundation,No.BK2010594
文摘Translational medicine pursues the conversion of scientific discovery into human health improvement.It aims to establish strategies for diagnosis and treatment of diseases.Cancer treatment is difficult.Radiopharmaceutical research has played an importantrole in multiple disciplines,particularly in translational oncology.Based on the natural phenomenon of necrosis avidity,Onco Ci Dia has emerged as a novel generic approach for treating solid malignancies.Under this systemic dual targeting strategy,a vascular disrupting agent first selectively causes massive tumor necrosis that is followed by iodine-131 labeled-hypericin(123IHyp),a necrosis-avid compound that kills the residual cancer cells by crossfire effect of beta radiation.In this review,by emphasizing the potential clinical applicability of Onco Ci Dia,we summarize our research activities including optimization of radioiodinated hypericin Hyp preparations and recent studies on the biodistribution,dosimetry,pharmacokinetic and,chemical and radiochemical toxicities of the preparations.Myocardial infarction is a global health problem.Although cardiac scintigraphy using radioactive perfusion tracers is used in the assessment of myocardial viability,searching for diagnostic imaging agents with authentic necrosis avidity is pursued.Therefore,a comparative study on the biological profiles of the necrosis avid 123I-Hyp and the commercially available 99mTc-Sestamibi was conducted and the results are demonstrated.Cholelithiasis or gallstone disease may cause gallbladder inflammation,infection and other severe complications.While studying the mechanisms underlying the necrosis avidity of Hyp and derivatives,their naturally occurring fluorophore property was exploited for targeting cholesterol as a main component of gallstones.The usefulness of Hyp as an optical imaging agent for cholelithiasis was studied and the results are presented.Multiple uses of automatic contrast injectors may reduce costs and save resources.However,cross-contaminations with bloodborne pathogens of infectious diseases may occur.We developed a radioactive method for safety evaluation of a new replaceable patient-delivery system.By mimicking pathogens with a radiotracer,we assessed the feasibility of using the system repeatedly without septic risks.This overview is deemed to be interesting to those involvedin the related fields for translational research.
基金Supported by Research Foundation-Flanders(FWO)the KU Leuven Molecular Small Animal Imaging Center Mo SAIC,No.KUL EF/05/08+4 种基金the center of excellence in vivo molecular imaging research(IMIR)KU Leuven projects,No.IOFHB/08/009 and No.IOF-HB/12/018the European Union,AsiaLink Cf P 2006-Europe Aid/123738/C/ACT/Multi-Proposal,No128-498/111National Natural Science Foundation of China,No.81071828Jiangsu Province Natural Science Foundation,No.BK2010594
文摘AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human gallstones.METHODS: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.
