The chemokine CXCR4 receptor is over-expressed in a wide variety of tumors.In this study,AMD3100,which was a prototype non-peptide antagonist of CXCR4 receptor,was labeled with;Tc.;Tc-AMD3100 was verified by thin laye...The chemokine CXCR4 receptor is over-expressed in a wide variety of tumors.In this study,AMD3100,which was a prototype non-peptide antagonist of CXCR4 receptor,was labeled with;Tc.;Tc-AMD3100 was verified by thin layer radio chromatography（TLRC）.The tumor-localizing properties of;Tc-AMD3100 were evaluated and proved in mice bearing Hep-G2 tumor xenograft.;Tc-AMD3100 was a promising,novel receptor-specific radiopharmaceutical with potential application in the imaging of human tumors.展开更多
Background:Drug-induced cardiomyopathy is a significant medical problem.Clinical diagnosis of myocardial injury is based on initial electrocardiogram,levels of circulating biomarkers,and perfusion imaging with single ...Background:Drug-induced cardiomyopathy is a significant medical problem.Clinical diagnosis of myocardial injury is based on initial electrocardiogram,levels of circulating biomarkers,and perfusion imaging with single photon emission computed tomography(SPECT).Positron emission tomography(PET)is an alternative imaging modality that provides better resolution and sensitivity than SPECT,improves diagnostic accuracy,and allows therapeutic monitoring.The objective of this study was to assess the detection of drug-induced cardiomyopathy by PET using 2-deoxy-2-[^18F]fluoro-D-glucose(FDG)and compare it with the conventional SPECT technique with[^99m Tc]-Sestamibi(MIBI).Methods:Cardiomyopathy was induced in Sprague Dawley rats using high-dose isoproterenol.Nuclear[^18F]FDG/PET and[^99m Tc]MIBI/SPECT were performed before and after isoproterenol administration.[^18F]FDG(0.1 mCi,200-400μL)and[^99m Tc]MIBI(2 mCi,200-600μL)were administered via the tail vein and imaging was performed 1 hour postinjection.Isoproterenol-induced injury was confirmed by the plasma level of cardiac troponin and triphenyltetrazolium chloride(TTC)staining.Results:Isoproterenol administration resulted in an increase in circulating cardiac troponin I and showed histologic damage in the myocardium.Visually,preisoproterenol and postisoproterenol images showed alterations in cardiac accumulation of[^18F]FDG,but not of[^99m Tc]MIBI.Image analysis revealed that myocardial uptake of[^18F]FDG reduced by 60%after isoproterenol treatment,whereas that of[^99m Tc]MIBI decreased by 45%.Conclusion:We conclude that[^18F]FDG is a more sensitive radiotracer than[^99m Tc]MIBI for imaging of drug-induced cardiomyopathy.We theorize that isoproterenolinduced cardiomyopathy impacts cellular metabolism more than perfusion,which results in more substantial changes in[^18F]FDG uptake than in[^99m Tc]MIBI accumulation in cardiac tissue.展开更多
A novel 99mTc labeled complex, [N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl) (2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]Technetium(V) oxide (PPPE-MAMA′-99mTcO) ([99mTc]-2) has been designed and p...A novel 99mTc labeled complex, [N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl) (2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]Technetium(V) oxide (PPPE-MAMA′-99mTcO) ([99mTc]-2) has been designed and prepared based on the integrated approach. The corresponding rhenium complex (PPPE-MAMA′-ReO)(Re-2) has been prepared and characterized. In vitro competi-tion binding assays show moderate affinity of Re-2 towards σ1 and σ2 receptors with Ki values of 8.67 ± 0.07 and 5.71 ± 1.88 μmol, respectively. Planar images obtained at 0.5 h, 4 h, 20 h after i.v. in-jection indicate the accumulation of [99mTc]-2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of [99mTc]-2 has been inhibited at 20 h after co-injection of [99mTc]-2 plus haloperidol (1 mg/kg). Biodistribution studies of [99mTc]-2 display an in vivo tumor uptake of 0.14% ± 0.01% ID/g at 24 h post i.v. injection with a tumor/muscle ratio of 6.02 ± 0.87. The above results suggest that [99mTc]-2, derived from a previously published lead compound, retains certain tumor uptake and affinity for σ receptors. [99mTc]-2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for σ receptors.展开更多
文摘The chemokine CXCR4 receptor is over-expressed in a wide variety of tumors.In this study,AMD3100,which was a prototype non-peptide antagonist of CXCR4 receptor,was labeled with;Tc.;Tc-AMD3100 was verified by thin layer radio chromatography（TLRC）.The tumor-localizing properties of;Tc-AMD3100 were evaluated and proved in mice bearing Hep-G2 tumor xenograft.;Tc-AMD3100 was a promising,novel receptor-specific radiopharmaceutical with potential application in the imaging of human tumors.
基金National Heart,Lung,and Blood Institute,Grant/Award Number:R41HL140919-01Sandra K.and David L.Gilliland Chair in Nuclear Pharmacy。
文摘Background:Drug-induced cardiomyopathy is a significant medical problem.Clinical diagnosis of myocardial injury is based on initial electrocardiogram,levels of circulating biomarkers,and perfusion imaging with single photon emission computed tomography(SPECT).Positron emission tomography(PET)is an alternative imaging modality that provides better resolution and sensitivity than SPECT,improves diagnostic accuracy,and allows therapeutic monitoring.The objective of this study was to assess the detection of drug-induced cardiomyopathy by PET using 2-deoxy-2-[^18F]fluoro-D-glucose(FDG)and compare it with the conventional SPECT technique with[^99m Tc]-Sestamibi(MIBI).Methods:Cardiomyopathy was induced in Sprague Dawley rats using high-dose isoproterenol.Nuclear[^18F]FDG/PET and[^99m Tc]MIBI/SPECT were performed before and after isoproterenol administration.[^18F]FDG(0.1 mCi,200-400μL)and[^99m Tc]MIBI(2 mCi,200-600μL)were administered via the tail vein and imaging was performed 1 hour postinjection.Isoproterenol-induced injury was confirmed by the plasma level of cardiac troponin and triphenyltetrazolium chloride(TTC)staining.Results:Isoproterenol administration resulted in an increase in circulating cardiac troponin I and showed histologic damage in the myocardium.Visually,preisoproterenol and postisoproterenol images showed alterations in cardiac accumulation of[^18F]FDG,but not of[^99m Tc]MIBI.Image analysis revealed that myocardial uptake of[^18F]FDG reduced by 60%after isoproterenol treatment,whereas that of[^99m Tc]MIBI decreased by 45%.Conclusion:We conclude that[^18F]FDG is a more sensitive radiotracer than[^99m Tc]MIBI for imaging of drug-induced cardiomyopathy.We theorize that isoproterenolinduced cardiomyopathy impacts cellular metabolism more than perfusion,which results in more substantial changes in[^18F]FDG uptake than in[^99m Tc]MIBI accumulation in cardiac tissue.
基金This work was supported by the National Natural Science Foundation of China (Grant Nos. 20471011 and 20501004).
文摘A novel 99mTc labeled complex, [N-[2-((2-oxo-2-(4-(3-phenylpropyl)piperazin-1-yl)ethyl) (2-mercaptoethyl)amino)acetyl]-2-aminoethanethiolato]Technetium(V) oxide (PPPE-MAMA′-99mTcO) ([99mTc]-2) has been designed and prepared based on the integrated approach. The corresponding rhenium complex (PPPE-MAMA′-ReO)(Re-2) has been prepared and characterized. In vitro competi-tion binding assays show moderate affinity of Re-2 towards σ1 and σ2 receptors with Ki values of 8.67 ± 0.07 and 5.71 ± 1.88 μmol, respectively. Planar images obtained at 0.5 h, 4 h, 20 h after i.v. in-jection indicate the accumulation of [99mTc]-2 in MCF-7 human breast tumor bearing mice at 20 h. Furthermore, the accumulation of [99mTc]-2 has been inhibited at 20 h after co-injection of [99mTc]-2 plus haloperidol (1 mg/kg). Biodistribution studies of [99mTc]-2 display an in vivo tumor uptake of 0.14% ± 0.01% ID/g at 24 h post i.v. injection with a tumor/muscle ratio of 6.02 ± 0.87. The above results suggest that [99mTc]-2, derived from a previously published lead compound, retains certain tumor uptake and affinity for σ receptors. [99mTc]-2 may be used as a basis for further structural modifications to develop tumor imaging agents with high affinity for σ receptors.
