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Mark A Green - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of Cu-PTSM as a tracer of tumor perfusion: Comparison with labeled microspheres in spontaneous canine neoplasms
Nuclear Medicine and Biology, 2004Co-Authors: Carla J Mathias, Mark A Green, W. B. Morrison, Deborah W. KnappAbstract:Abstract Copper-62-labeled Cu-PTSM is a promising generator-produced PET tracer for myocardial, cerebral and renal perfusion. To evaluate whether [ 62 Cu]Cu-PTSM could also serve as a blood flow tracer in PET studies of tumor tissue, the tumor uptake of [ 67 Cu]Cu-PTSM was examined in dogs with spontaneously-occurring soft-tissue neoplasms. Copper-67-labeled Cu-PTSM was administered intravenously to four anesthetized dogs, followed c. 5 min later by a left ventricular injection of 85 Sr-labeled microspheres (15 μm) to provide an independent measure of tumor perfusion. Forty-seven tumors (average weight=2.5 ± 3.7 g) were obtained and sectioned into 80 samples. The correlation of 67 Cu-PTSM uptake with regional renal perfusion was also examined in data from 395 tissue samples ranging in flow from 0.02 to 9.39 mL min −1 g −1 . Rates of tumor perfusion assessed with 85 Sr-labeled microspheres ranged from 0.011 to 3.0 mL min −1 g −1 . No correlation was found between tumor size and the rate of tumor perfusion. However, an excellent linear correlation exists between tumor perfusion calculated from [ 67 Cu]Cu-PTSM data and tumor perfusion measured with 85 Sr-microspheres ( r = 0.94 for 80 samples), suggesting that [ 62 Cu]Cu-PTSM may be useful as a radiopharmaceutical for PET studies of tumor perfusion.
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Copper 62 pyruvaldehyde bis n4 methyl thiosemicarbazone pet imaging in the detection of coronary artery disease in humans
Journal of Nuclear Cardiology, 2001Co-Authors: Thomas R Wallhaus, Mark A Green, Jeffrey L Lacy, Richard Stewart, Jesus A Bianco, Nisha Nayak, Charles K StoneAbstract:Background Copper-62 (II)-pyruvaldehyde bis(N4-methyl-thiosemicarbazone) (PTSM) has been proposed for cardiac imaging with positron emission tomography (PET). This study evaluated the agreement between Cu-62-PTSM and coronary angiography in the detection of occlusive coronary artery disease. The normalcy rate for Cu-62-PTSM PET in a group of healthy volunteers was also assessed.
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Copper-62-pyruvaldehyde bis(N^4-methyl-thiosemicarbazone) PET imaging in the detection of coronary artery disease in humans
Journal of Nuclear Cardiology, 2001Co-Authors: Thomas R Wallhaus, Mark A Green, Richard Stewart, Nisha Nayak, Jeffrey Lacy, Jesus Bianco, Charles K StoneAbstract:Background Copper-62 (II)-pyruvaldehyde bis(N^4-methyl-thiosemicarbazone) (PTSM) has been proposed for cardiac imaging with positron emission tomography (PET). This study evaluated the agreement between Cu-62-PTSM and coronary angiography in the detection of occlusive coronary artery disease. The normalcy rate for Cu-62-PTSM PET in a group of healthy volunteers was also assessed. Methods and Results Forty-five subjects completed the study. Twenty-eight patients underwent stress technetium-99m sestamibi single photon emission computed tomography (SPECT) imaging and cardiac catheterization followed by Cu-62-PTSM rest/dipyridamole stress PET scans, and 17 volunteers underwent Cu-62-PTSM rest/dipyridamole stress PET scans. Cu-62-PTSM myocardial perfusion defects were identified in 100% of patients with 3-vessel disease (n = 8), 100% of patients with 2-vessel disease (n = 9), and 67% of patients with single-vessel disease (n = 6). When considering individual vessels, Cu-62-PTSM perfusion defects were seen in 72% of patients with occlusive disease in the left anterior descending artery territory, 67% in the left circumflex artery territory, and 60% in the right coronary artery territory, respectively. All 17 healthy volunteers had Cu-62-PTSM scans interpreted as normal, for a normalcy rate of 100%. Conclusions Perfusion abnormalities are demonstrated by means of Cu-62-PTSM PET in 91% of patients with occlusive coronary artery disease seen at the time of cardiac catheterization, and it shows an excellent normalcy rate of 100%.
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human biodistribution and dosimetry of the pet perfusion agent Copper 62 ptsm
The Journal of Nuclear Medicine, 1998Co-Authors: Thomas R Wallhaus, Mark A Green, Jeffrey L Lacy, Jean Whang, Robert J Nickles, Charles K StoneAbstract:UNLABELLED: Copper-62-pyruvaldehyde bis(N4-methyl)thiosemicarbazone (PTSM) has been proposed as a generator-produced radiopharmaceutical for perfusion imaging using PET. Several clinical studies have demonstrated the ability of 62Cu-PTSM to quantitate myocardial and cerebral perfusion in humans. Because 62Cu-PTSM is generator-produced, it can be provided to clinical centers without cyclotron availability and, therefore, represents a cost-effective, practical PET perfusion tracer for clinical applications. To assess the safety, time-dependent biodistribution, and whole-body and organ-specific absorbed radiation dose estimates of this tracer, a Phase I study of 62Cu-PTSM was performed using whole-body imaging with PET in 10 healthy volunteers and with the radiopharmaceutical delivered by a compact modular generator unit. METHODS: Five male and five female subjects underwent a series of clinical tests and head-to-midthigh, whole-body PET scans at three time points over 1 hr after intravenous injection of 62Cu-PTSM. Before injection of the tracer, PET transmission scans were performed and used to correct the emission data for attenuation. Final image data were expressed in units of mCi/cc. Using standard organ weights, the percent injected dose per organ was calculated. Biodistribution data were obtained at three different time points and from these data biological half-lives in different organs were determined for calculation of radiation absorbed dose estimates. RESULTS: The liver was seen as the critical organ receiving a dose of 0.0886 rad/mCi. This organ defined the maximum single injected dose at 56 mCi using the limit of 5 rads to a critical organ per study per year. The whole-body dose is 0.0111 rad/mCi, resulting in a 0.622 rad exposure with a maximum single injection dose. Only trace levels of activity were found in the urine, which suggests low levels of urinary excretion and bladder exposure. No significant clinical, electrocardiographic or laboratory abnormalities were seen after the injection of 62Cu-PTSM. CONCLUSION: Copper-62-PTSM is a clinically safe radiopharmaceutical with favorable dosimetry for human studies at injected doses significantly above those projected for use in clinical studies.
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Copper 62 radiopharmaceuticals for diagnostic imaging with positron emission tomography pet
Transition Metal Chemistry, 1997Co-Authors: Mark A GreenAbstract:Summary Bis(thiosemicarbazone) complexes of short-lived Copper-62 may find clinical use as imaging agents for evaluation of myocardial and cerebral blood flow with positron emission tomography. Three of the most promising of these Copper(II) radiopharmaceuticals are the complexes of pyruvaldehyde bisON 4 -methylthiosemicarbazone)(PTSM);ethylglyoxal bis(thiosemicarbazone) (ETS); and n-propylglyoxal bis(thiosemicarbazone) On-PrTS). Positron emission tomography (PET) is a medical imaging technique that can quantitatively map radiopharmaceutical concentrations inside the living body (1,2) . PET allows non-invasive assessment of various aspects of tissue biochemistry and pathophysiology through direct observation of regional drug distribution and pharmacokinetics. A radiopharmaceutical used as a probe of tissue function with PET must be labelled with a radionuclide that decays with emission of a positron Ob a ; a positively charged electron). The most commonly used positron-emitting nuclides are cyclotron-produced
Steven R Bergmann - One of the best experts on this subject based on the ideXlab platform.
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regional myocardial perfusion assessed with generator produced Copper 62 ptsm and pet
The Journal of Nuclear Medicine, 1996Co-Authors: Pilar Herrero, Carolyn J. Anderson, Michael J. Welch, Judy J Hartman, Mark Green, Joanne Markham, Steven R BergmannAbstract:We have previously demonstrated that myocardial perfusion can be estimated accurately in experimental animals with the generator-produced positron-emitting tracer, 62 Cu-pyruvaldehyde bis (N 4 -methylthio-semicarbazone)( 62 Cu-PTSM) and PET. This study evaluated the feasibility of quantifying regional myocardial blood flow using 62 Cu-PTSM and PET in human subjects. Methods : Regional perfusion was estimated using a previously described and validated two-compartment model from dynamic PET scans obtained after an intravenous bolus of 62 Cu-PTSM in 10 healthy volunteers and in 6 patients with coronary artery disease at rest ; and in 9 of the volunteers and 4 of the patients after administration of dipyridamole intravenously. Flow estimates were compared with those obtained using H 2 15 O. Results : Contrast was high between myocardium and blood or lung with 62 Cu-PTSM, resulting in high-quality myocardial images. Over uptake was also high. At flows of up to 1.5 ml/g/min, flow estimated with 62 Cu-PTSM correlated closely with estimates obtained with H 2 15 O (y = 0.71x + 0.21, n = 169 regional comparisons, r = 0.66, p < 0.05), but this relationship was not maintained at higher flows. Conclusion : The results demonstrate that quantification of myocardial perfusion with 62 Cu-PTSM is feasible in human subjects but cannot be used to estimate hyperemic flows due most likely to the strong binding of the tracer to human serum albumin. Copper-62-PTSM congeners with less avidity for human albumin may prove more suitable for evaluation of hyperemic flows.
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Species-Dependent Binding of Copper(II) Bis(Thiosemicarbazone) Radiopharmaceuticals to Serum Albumin
The Journal of Nuclear Medicine, 1995Co-Authors: Carla J Mathias, Steven R Bergmann, Mark GreenAbstract:Copper-62-labeled pyruvaldehyde bis(N 4 -methylthiosemicarbazonato)-Copper(ll) (Cu-PTSM) is a generator-based PET radiopharmaceutical under investigation for use in evaluation of tissue perfusion. Despite promising results from animals, problems have been encountered in the use of 62 Cu-PTSM to quantitate myocardial perfusion in humans at high flow rates, possibly due to species-dependent interactions of the tracer with serum albumin. Methods : Ultrafiltration and plasma/erythrocyte partitioning studies were performed to assess the protein binding of 67 Cu-labeled Cu-PTSM and six related Copper(II) bis(thiosemicarbazone) complexes. Results : These studies reveal significant interspecies variability in the strength of Cu-PTSM binding to serum albumin, with 67 Cu-PTSM binding much more strongly to human albumin than to dog albumin. Most of the related Cu(II)-bis(thiosemicarbazone) complexes examined exhibit interspecies variability of albumin binding similar to that observed with Cu-PTSM. Two such complexes, Cu-ETS and Cu-n-PrTS, however, were identified that exhibit no preferential association with human serum albumin. Conclusion : Copper-62-PTSM exhibits substantial interspecies variability in the strength of its binding to serum albumin, which appears to explain the problems encountered in using animal data to predict 62 Cu-PTSM behavior in humans. The 62 Cu-ETS and 62 Cu-n-PrTS complexes may be viable alternatives to 62 Cu-PTSM for PET studies to evaluate quantitatively myocardial blood flow in humans.
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in vivo comparison of Copper blood pool agents potential radiopharmaceuticals for use with Copper 62
The Journal of Nuclear Medicine, 1991Co-Authors: Carta J Mathias, Michael J. Welch, Mark A Green, Habibe Diril, Claude F Meares, Robert J Gropler, Steven R BergmannAbstract:: Two techniques for labeling of albumin with Copper-67 (67Cu) and 62Cu were investigated; one using the native Cu(II) binding site of the protein and the other employing a bifunctional chelate, 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane- N,N'N",N"'-tetraacetic acid (Br-benzyl-TETA or BAT), conjugated to the protein. Rat biodistribution experiments with 67Cu demonstrated retention of i.v. 67Cu-benzyl-TETA-albumin in the blood pool identical to co-injected 125I-albumin. By contrast, i.v. administration of either [67Cu]-Cu-acetate or [67Cu]-Cu-acetate pre-mixed with albumin results in relatively rapid clearance of blood-pool radioactivity as the tracer is excreted into the urine. The 62Cu-benzyl-TETA-albumin radiopharmaceutical was obtained in ca. 17% radiochemical yield (end of synthesis, without decay correction) following a procedure that can be completed in 15-18 min. In PET experiments with a baboon, myocardial blood volume images with 62Cu-benzyl-TETA-albumin were identical to those obtained with C15O. Use of the 62Cu-benzyl-TETA-albumin image for blood-pool subtraction of a 62Cu-PTSM myocardial perfusion image is illustrated. Copper-62-benzyl-TETA-HSA should be a useful, generator-produced radiotracer for the detection of the vascular pool at PET facilities without cyclotrons.
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Copper 62 labeled pyruvaldehyde bis n4 methylthiosemicarbazonato Copper ii synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion
The Journal of Nuclear Medicine, 1990Co-Authors: Mark A Green, Carla J Mathias, M J Welch, Andrea H Mcguire, David Perry, Frankee Fernandezrubio, Joel Perlmutter, Marcus E Raichle, Steven R BergmannAbstract:: Generator produced positron-emitting radionuclides could potentially expand the application of positron emission tomography (PET) to centers that do not have access to a local cyclotron. The zinc-62/Copper-62 radionuclide generator system could serve as a source of positron-emitting Copper-62 (62Cu) (t1/2 = 9.74 min) for physiologic imaging. Accordingly, we have prepared zinc-62/Copper-62 generators capable of high output (greater than 300 mCi) and used the no-carrier-added eluate in a rapid high yield synthesis of [62Cu] Cu(PTSM) that provides the radiopharmaceutical in a form suitable for intravenous injection (where Cu(PTSM) = pyruvaldehyde bis(N4-methylthiosemicarbazonato) Copper(II]. We then demonstrated in pilot studies that [62Cu]Cu(PTSM) provides high quality brain and heart images with PET, accurately delineating cerebral and myocardial perfusion in both experimental animals and in humans (corroborating results of previous experimental studies utilizing longer-lived Copper isotopes). The results of this work demonstrate that 62Cu can be conveniently obtained from high-level generators and, when used to label Cu(PTSM), provides a generator-produced radiopharmaceutical capable of providing estimates of cerebral and myocardial perfusion independent of cyclotron-produced radionuclides.
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Assessment of regional myocardial and renal blood flow with Copper-PTSM and positron emission tomography.
Circulation, 1990Co-Authors: Marc E. Shelton, Michael J. Welch, Mark A Green, Carla J Mathias, Steven R BergmannAbstract:We recently demonstrated in isolated, perfused hearts that radiolabeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)Copper(II) (Cu-PTSM) is well extracted throughout a range of conditions including ischemia, hypoxia, and hyperemia. Once extracted, binding of radioactivity by the isolated heart was essentially irreversible, giving this tracer microspherelike qualities. Because Cu-PTSM can be readily prepared with the generator-produced positron-emitting Copper 62 and other gamma- or positron-emitting Copper radionuclides, we evaluated its usefulness for measuring regional myocardial and renal blood flow in vivo in intact dogs at rest, after ischemia, or after coronary hyperemia was induced by intravenous administration of dipyridamole. After intravenous administration of radiolabeled Cu-PTSM, the tracer cleared rapidly from the blood. Myocardial uptake of single photon-emitting 67Cu-labeled Cu-PTSM was measured directly in myocardial samples 15 minutes after tracer administration, and it increased proportionally with blood flow throughout the flow range (estimated concomitantly with radiolabeled microspheres) of 0.0-6.0 ml/g/min (n = 340 samples from 17 dogs, r = 0.99, YCopper radioactivity = 85Xmicrosphere flow -7 chi 2 + 17). Renal uptake of radiolabeled Cu-PTSM was also proportional to blood flow. Positron emission tomography was performed in four intact dogs after intravenous administration of 64Cu-labeled Cu-PTSM (19% positron decay, t1/2 = 12.8 hours). High-quality images of heart and kidney were obtained. Accordingly, radiolabeled Cu-PTSM should be a useful, generator-produced tracer for estimating regional myocardial and renal blood flow with positron emission tomography.
Junji Konishi - One of the best experts on this subject based on the ideXlab platform.
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Application of the new zinc-62/Copper-62 generator: an effective labeling method for 62Cu-PTSM.
International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology, 2004Co-Authors: Kazuya Matsumoto, Junji Konishi, Yasuhisa Fujibayashi, Yoshiharu Yonekura, Kouichi Wada, Yasutaka Takemura, Akira YokoyamaAbstract:Abstract A potential PET flow tracer, 62 Cu-labeled pyruvaldehyde bis(N 4 -methylthiosemicarbazone) ( 62 Cu-PTSM), was prepared using a new 62 Zn/ 62 Cu generator. With this 62 Cu-labeling method based on a ligand exchange reaction, 62 Cu-PTSM was quantitatively obtained by simple mixing of the generator eluate, 62 Cu-glycine and PTSM solution for a few seconds. The glycine contained in the 62 Cu-PTSM injectate had no significant effect in mouse biodistribution studies. The PET studies of 62 Cu-PTSM showed brain images that were not visualized by 62 Cu-labeled albumin (a plasma pool tracer), in the dog cranium.
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Copper 62 atsm a new hypoxia imaging agent with high membrane permeability and low redox potential
The Journal of Nuclear Medicine, 1997Co-Authors: Yasuhisa Fujibayashi, Hideyuki Taniuchi, Hiroshi Ohtani, Junji Konishi, Yoshiharu Yonekura, Akira YokoyamaAbstract:An ideal hypoxia imaging agent should have high membrane permeability for easy access to intracellular mitochondria and low redox potential to confer stability in normal tissue, but it should be able to be reduced by mitochondria with abnormally high electron concentrations in hypoxic cells. In this context, nitroimidazole residues are not considered to be essential. In this study, Cu(II)-diacetyl-bis(N 4 -methylthiosemicarbazone) (Cu-ATSM), a 62Cu-bisthiosemicarbazone complex, with high membrane permeability and low redox potential, was evaluated as a possible hypoxia imaging agent, using electron spin resonance spectrometry and the Langendorff isolated perfused rat heart model as well as rat heart left anterior descending occlusion model. Methods: Nonradioactive Cu-ATSM was incubated with rat mitochondria, after which reduction of Cu(II) to Cu(I) was measured with electron spin resonance. As a model of hypoxic mitochondria, rotenone (Complex I inhibitor)-treated mitochondria were used. Results: In this study, Cu-ATSM was reduced by hypoxic but not by normal mitochondria. Conclusion: Thus, retention of 62 Cu-ATSM was studied serially in perfused rat hearts under conditions of normoxia (95% O 2 + 5% CO 2 ), hypoxia (95% N 2 + 5% CO 2 ) and reoxygenation (95% O 2 + 5% CO 2 ). In normoxia and reoxygenation, 62 Cu-ATSM injected as a single bolus showed low retention (23.77% and 22.80%, respectively) 15 min after injection, but retention was increased markedly under hypoxic conditions (81.10%). Also, in the in vivo left anterior descending occluded rat heart model, 62 Cu-ATSM retention was inversely correlated with accumulation of 201 Tl, a relative myocardial blood flow marker.
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hyperfixation of Copper 62 ptsm in rat brain after transient global ischemia
The Journal of Nuclear Medicine, 1997Co-Authors: Hideyuki Taniuchi, Junji Konishi, Yasuhisa Fujibayashi, Yoshiharu Yonekura, Akira YokoyamaAbstract:We evaluated the regional distribution of 62 Cu-pyruvaldehyde bis(N 4 -methylthiosemicarbazone) ( 62 Cu-PTSM), a potential PET perfusion agent, in the rat brain and observed hyperfixation in transient global ischemia in rats. Methods: The distribution of 62 Cu-PTSM was examined in comparison with that of 123 I-labelec p-iodophenyl-N-isopropylmethanphetamine ( 123 I-IMP) as a reference blood flow marker. Brain uptake of these two tracers was measured in Wistar rats subjected to 30-min four-vessel occlusion followed by recirculation for 10 min, 1 hr or 1, 3 or 5 days. Tracers were injected intravenously into rats 10 min before decapitation. The activities of Complex I and Complex I-III of mitochondria and the concentration of sulfhydryl (SH) groups were also measured. Results: Copper-62-PTSM showed accelerated accumulation in the brain at 1 hr and 1 day after reperfusion when compared with that of 123 I-IMP (p < 0.01), and this enhancement was considered to be due to hyperfixation. At these time points, SH concentration was significantly decreased (p < 0.01). On the other hand, the activity of Complex I was not influenced by ischemia/reperfusion, but that of Complex I-III was decreased to 65-70% of the control level (p < 0.01). Conclusion: Copper-62-PTSM showed hyperfixation most possibly as a result of increased NADH concentration, caused by disturbed electron transport in mitochondria.
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measurement of regional cerebral blood flow with Copper 62 ptsm and a three compartment model
The Journal of Nuclear Medicine, 1996Co-Authors: Hidehiko Okazawa, Yasuhisa Fujibayashi, Yoshiharu Yonekura, Sadahiko Nishizawa, Koichi Ishizu, Yasuhiro Magata, Nagara Tamaki, T Mukai, Junji KonishiAbstract:We evaluated quantitatively 62 Cu-labeled pyruvaldehyde bis(N 4 -methylthiosemicarbazone) Copper II ( 62 Cu-PTSM) as a brain perfusion tracer for positron emission tomography (PET). For quantitative measurement, the octanol extraction method is needed to correct for arterial radioactivity in estimating the lipophilic input function, but the procedure is not practical for clinical studies. To measure regional cerebral blood flow (rCBF) by 62 Cu-PTSM with simple arterial blood sampling, a standard curve of the octanol extraction ratio and a three-compartment model were applied. Methods : We performed both 15 O-labeled water PET and 62 Cu-PTSM PET with dynamic data acquisition and arterial sampling in six subjects. Data obtained in 10 subjects studied previously were used for the standard octanol extraction curve. Arterial activity was measured and corrected to obtain the true input function using the standard curve. Results : Graphical analysis (Gjedde-Patlak plot) with the data for each subject fitted by a straight regression line suggested that 62 Cu-PTSM can be analyzed by the three-compartment model with negligible k 4 . Using this model, K 1 -k 3 were estimated from curve fitting of the cerebral time-activity curve and the corrected input function. The fractional uptake of 62 Cu-PTSM was corrected to rCBF with the individual extraction at steady state calculated from K 1 -k 3 . The influx rates (K i ) obtained from three-compartment model and graphical analyses were compared for the validation of the model. A comparison of rCBF values obtained from 62 Cu-PTSM and 15 O-water studies demonstrated excellent correlation. Conclusion : The results suggest the potential feasibility of quantitation of cerebral perfusion with 62 Cu-PTSM accompanied by dynamic PET and simple arterial sampling.
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generator produced Copper 62 ptsm as a myocardial pet perfusion tracer compared with nitrogen 13 ammonia
The Journal of Nuclear Medicine, 1996Co-Authors: Eiji Tadamura, Yasuhisa Fujibayashi, Yoshiharu Yonekura, Hidehiko Okazawa, Yasuhiro Magata, Nagara Tamaki, Takashi Kudoh, Ryuji Nohara, Shigetake Sasayama, Junji KonishiAbstract:The purpose of this study was to determine the suitability of 62 Cu-pyruvaldehyde bis(N 4 -methylthiosemicarbazone) ( 62 Cu-PTSM) for estimating myocardial blood flow (MBF) over a wide range of flow by comparison with 13 N-ammonia ( 13 NH 3 ). Methods : PET studies using 62 Cu-PTSM and 13 NH 3 were performed at rest and after pharmacological vasodilatation in 9 normal subjects and 13 patients with coronary artery disease (CAD). According to the microsphere method, values for the product of the extraction fraction and MBF (ExMBF) were calculated using both tracers. In static images, the percent uptake (normalized to the peak count) of each tracer was measured in patients with CAD. Results : The myocardial tracer distribution in the normal subjects was significantly higher in the inferior wall in the 62 Cu-PTSM studies and lower in the lateral wall in the 13 NH 3 studies. The ExMBF values showed linear correlation for both tracers in a low flow range. In a high flow range, however, the ExMBF values for 62 Cu-PTSM were nonlinearly proportional to the increase of those for 13 NH 3 (y = 1.1x-0.21x 2 , r = 0.81). The percent uptake for both tracers at baseline well correlated linearly (y = 10.4 + 0.88x, R = 0.91). After pharmacological vasodilatation underestimation of blood flow with 62 Cu-PTSM was noted compared to that with 13 NH 3 at high flows (y = 31.8 + 0.63x, r = 0.76). Conclusion : These results suggest that the MBF estimates using 62 Cu-PTSM in a low flow range may be as accurate as those with 13 NH 3 . In a high flow range, however, the extraction fraction of 62 Cu-PTSM is considered to be lower than that of 13 NH S , and this may limit the estimation of MBF with 62 Cu-PTSM after pharmacological vasodilatation.
Yasuhisa Fujibayashi - One of the best experts on this subject based on the ideXlab platform.
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Application of the new zinc-62/Copper-62 generator: an effective labeling method for 62Cu-PTSM.
International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology, 2004Co-Authors: Kazuya Matsumoto, Junji Konishi, Yasuhisa Fujibayashi, Yoshiharu Yonekura, Kouichi Wada, Yasutaka Takemura, Akira YokoyamaAbstract:Abstract A potential PET flow tracer, 62 Cu-labeled pyruvaldehyde bis(N 4 -methylthiosemicarbazone) ( 62 Cu-PTSM), was prepared using a new 62 Zn/ 62 Cu generator. With this 62 Cu-labeling method based on a ligand exchange reaction, 62 Cu-PTSM was quantitatively obtained by simple mixing of the generator eluate, 62 Cu-glycine and PTSM solution for a few seconds. The glycine contained in the 62 Cu-PTSM injectate had no significant effect in mouse biodistribution studies. The PET studies of 62 Cu-PTSM showed brain images that were not visualized by 62 Cu-labeled albumin (a plasma pool tracer), in the dog cranium.
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Copper-62 ATSM as a hypoxic tissue tracer in myocardial ischemia
Annals of Nuclear Medicine, 2001Co-Authors: Norio Takahashi, Yasuhisa Fujibayashi, Yoshiharu Yonekura, Michael J. Welch, Atsuo Waki, Tatsuro Tsuchida, Norihiro Sadato, Katsuya Sugimoto, Akira Nakano, Harumi ItohAbstract:Copper-62 labeled diacetyl-bis ( N ^4-methylthiosemicarbazone) (^62Cu-ATSM) has been proposed as a generator produced positron-emitting tracer for hypoxic tissue imaging. To clarify the usefulness of^62Cu-ATSM for myocardial ischemia,^62Cu-ATSM PET was performed in 7 patients with coronary artery disease. Increased myocardial uptake of^62Cu-ATSM was observed (myocardium/blood ratio: 3.09) in one patient with unstable angina, who had increased^18F-fluorodeoxyglucose (^18F-FDG) uptake under the fasting condition. The other 6 patients, who were clinically stable, did not have increased^62Cu-ATSM uptake, although abnormal^18F-FDG uptake was seen in 4 patients. This preliminary study suggests that^62Cu-ATSM is a promising PET tracer for hypoxic imaging in acute ischemia.
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Copper 62 atsm a new hypoxia imaging agent with high membrane permeability and low redox potential
The Journal of Nuclear Medicine, 1997Co-Authors: Yasuhisa Fujibayashi, Hideyuki Taniuchi, Hiroshi Ohtani, Junji Konishi, Yoshiharu Yonekura, Akira YokoyamaAbstract:An ideal hypoxia imaging agent should have high membrane permeability for easy access to intracellular mitochondria and low redox potential to confer stability in normal tissue, but it should be able to be reduced by mitochondria with abnormally high electron concentrations in hypoxic cells. In this context, nitroimidazole residues are not considered to be essential. In this study, Cu(II)-diacetyl-bis(N 4 -methylthiosemicarbazone) (Cu-ATSM), a 62Cu-bisthiosemicarbazone complex, with high membrane permeability and low redox potential, was evaluated as a possible hypoxia imaging agent, using electron spin resonance spectrometry and the Langendorff isolated perfused rat heart model as well as rat heart left anterior descending occlusion model. Methods: Nonradioactive Cu-ATSM was incubated with rat mitochondria, after which reduction of Cu(II) to Cu(I) was measured with electron spin resonance. As a model of hypoxic mitochondria, rotenone (Complex I inhibitor)-treated mitochondria were used. Results: In this study, Cu-ATSM was reduced by hypoxic but not by normal mitochondria. Conclusion: Thus, retention of 62 Cu-ATSM was studied serially in perfused rat hearts under conditions of normoxia (95% O 2 + 5% CO 2 ), hypoxia (95% N 2 + 5% CO 2 ) and reoxygenation (95% O 2 + 5% CO 2 ). In normoxia and reoxygenation, 62 Cu-ATSM injected as a single bolus showed low retention (23.77% and 22.80%, respectively) 15 min after injection, but retention was increased markedly under hypoxic conditions (81.10%). Also, in the in vivo left anterior descending occluded rat heart model, 62 Cu-ATSM retention was inversely correlated with accumulation of 201 Tl, a relative myocardial blood flow marker.
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hyperfixation of Copper 62 ptsm in rat brain after transient global ischemia
The Journal of Nuclear Medicine, 1997Co-Authors: Hideyuki Taniuchi, Junji Konishi, Yasuhisa Fujibayashi, Yoshiharu Yonekura, Akira YokoyamaAbstract:We evaluated the regional distribution of 62 Cu-pyruvaldehyde bis(N 4 -methylthiosemicarbazone) ( 62 Cu-PTSM), a potential PET perfusion agent, in the rat brain and observed hyperfixation in transient global ischemia in rats. Methods: The distribution of 62 Cu-PTSM was examined in comparison with that of 123 I-labelec p-iodophenyl-N-isopropylmethanphetamine ( 123 I-IMP) as a reference blood flow marker. Brain uptake of these two tracers was measured in Wistar rats subjected to 30-min four-vessel occlusion followed by recirculation for 10 min, 1 hr or 1, 3 or 5 days. Tracers were injected intravenously into rats 10 min before decapitation. The activities of Complex I and Complex I-III of mitochondria and the concentration of sulfhydryl (SH) groups were also measured. Results: Copper-62-PTSM showed accelerated accumulation in the brain at 1 hr and 1 day after reperfusion when compared with that of 123 I-IMP (p < 0.01), and this enhancement was considered to be due to hyperfixation. At these time points, SH concentration was significantly decreased (p < 0.01). On the other hand, the activity of Complex I was not influenced by ischemia/reperfusion, but that of Complex I-III was decreased to 65-70% of the control level (p < 0.01). Conclusion: Copper-62-PTSM showed hyperfixation most possibly as a result of increased NADH concentration, caused by disturbed electron transport in mitochondria.
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measurement of regional cerebral plasma pool and hematocrit with Copper 62 labeled hsa dts
The Journal of Nuclear Medicine, 1996Co-Authors: Hidehiko Okazawa, Yasuhisa Fujibayashi, Yoshiharu Yonekura, Sadahiko Nishizawa, Hiroshi Yamauchi, Koichi Ishizu, Yasuhiro Magata, Nagara Tamaki, Hidenao Fukuyama, Akira YokohamaAbstract:We developed Copper-62-labeled human serum albumin-dithiosemicarbazone ( 62 Cu-HSA-DTS) as a blood-pool imaging agent for PET. To evaluate 62 Cu-HSA-DTS for plasma-pool imaging and to measure the regional cerebral hematocrit, 12 normal volunteers and 7 patients with cerebrovascular disease underwent PET studies with 62 Cu-HSA-DTS and 15 O-labeled carbon monoxide (C 15 O). Methods : The normal subjects were studied with both C 15 O and 62 Cu-HSA-DTS. All patients were examined by 15 O-gas studies to measure cerebral perfusion and oxygen metabolism, followed by measurement of plasma volume with 62 Cu-HSA-DTS for analysis of regional cerebral hematocrit. Regional cerebral hematocrit was calculated from regional cerebral red cell volume (rCRCV) measured by C 15 O and regional plasma volume (rCPV) measured by 62 Cu-HSA-DTS in each subject, and the regional cerebral/large-vessel hematocrit ratio was obtained for both cerebral hemispheres in each subject. Results : Mean regional cerebral hematocrit and mean cerebral/large-vessel hematocrit ratio in the 12 normal volunteers were 38.3 ± 3.45% and 0.88 ± 0.06, respectively. In the seven patients with cerebrovascular disease, regional cerebral hematocrit was significantly lower on the hypoperfused side than the normal hemisphere. The images of rCPV and rCRCV from these patients demonstrated a greater increase in rCPV than rCRCV in the hypoperfused area. Conclusion : These results suggest that 62 Cu-HSA-DTS can be used for measurement of plasma volume and that regional cerebral hematocrit may provide valuable information regarding the microcirculation in the brain.
Markus Schwaiger - One of the best experts on this subject based on the ideXlab platform.
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heterogeneity of regional nitrogen 13 labeled ammonia tracer distribution in the normal human heart comparison with rubidium 82 and Copper 62 labeled ptsm
Journal of Nuclear Cardiology, 1994Co-Authors: Rob S Beanlands, Otto Muzik, Gary D Hutchins, Edwin R. Wolfe, Markus SchwaigerAbstract:Background Recent reports on13N-labeled ammonia (13N-ammonia) positron emission tomographic (PET) imaging have suggested a relative reduction of measured tracer activity in the posterolateral wall. Such inhomogeneity of tracer distribution could potentially affect accuracy for detection of disease. The aim of this study was to compare the regional distribution of13N-ammonia with82Rb and62Cu-labeled PTSM (62Cu-PTSM) to identify tracer-specific patterns that may be important in the clinical interpretation of cardiac flow studies.
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Heterogeneity of regional nitrogen 13-labeled ammonia tracer distribution in the normal human heart: Comparison with rubidium 82 and Copper 62-labeled PTSM
Journal of Nuclear Cardiology, 1994Co-Authors: Rob S. B. Beanlands, Otto Muzik, Gary D Hutchins, Edwin R. Wolfe, Markus SchwaigerAbstract:Background Recent reports on^13N-labeled ammonia (^13N-ammonia) positron emission tomographic (PET) imaging have suggested a relative reduction of measured tracer activity in the posterolateral wall. Such inhomogeneity of tracer distribution could potentially affect accuracy for detection of disease. The aim of this study was to compare the regional distribution of^13N-ammonia with^82Rb and^62Cu-labeled PTSM (^62Cu-PTSM) to identify tracer-specific patterns that may be important in the clinical interpretation of cardiac flow studies. Methods and Results Twenty-eight healthy volunteers underwent PET imaging at rest with either^13N-ammonia ( n =14),^82Rb ( n =8), or^62Cu-PTSM ( n =6). Eight subjects given^13N-ammonia also underwent imaging after adenosine. Activity measured in the posterolateral wall on transaxial images was significantly lower than in the septum for^13N-ammonia, both at rest ( p
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the kinetics of Copper 62 ptsm in the normal human heart
The Journal of Nuclear Medicine, 1992Co-Authors: Rob S Beanlands, Otto Muzik, Mark A Mintun, Thomas J Mangner, Neil A Petry, Gary D Hutchins, Markus SchwaigerAbstract:: Copper-62-labeled pyruvaldehyde bis(N-4-methylthiosemicarbazone) Copper(II) (PTSM) is a generator-produced myocardial perfusion tracer. Animal studies have shown high myocardial tissue extraction and prolonged retention. The aim of this study was to define myocardial kinetics of 62Cu-PTSM and to determine its suitability for evaluating myocardial perfusion at rest and during pharmacological vasodilation in human subjects. In six healthy volunteers, 62Cu-PTSM was administered at baseline and during a 6-min adenosine infusion (140 micrograms/kg/min). Dynamic PET imaging with high temporal resolution was performed over 20 min. Good image quality was observed at rest and following adenosine. Myocardial kinetics demonstrated prolonged tissue retention with a clearance half-life of 105 +/- 49 min at rest and 101 +/- 65 min following adenosine (p = ns). Copper-62-PTSM tissue retention was quantified and showed only a 1.97-fold increase from rest to adenosine studies. This suggests attenuation of tracer retention at high flow rates. Copper-62-PTSM represents a promising new radiopharmaceutical for the evaluation of myocardial perfusion in the human heart.
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Assessment of myocardial perfusion by positron emission tomography.
American Journal of Cardiology, 1991Co-Authors: Markus Schwaiger, Otto MuzikAbstract:Positron emission tomography (PET) represents an advanced imaging technology for the noninvasive evaluation of regional myocardial blood flow. Several blood flow tracers are available, including cyclotron-produced radiopharmaceuticals such as [ 15 O]H 2 O and [ 13 N]NH 3 and generator-produced rubidium-82 ([ 82 Rb]-) and Copper-62 ([ 62 Cu]-) pyruvaldehyde- bis -( N -4-methylthiosemicarbazone) (PTSM). 82 Rb and [ 13 N]NH 3 are the most commonly employed tracers for the qualitative evaluation of regional myocardial perfusion. Their use allows the accurate detection of coronary artery disease in combination with pharmacologic stress. Initial comparative studies with thallium-201 ( 201 Tl) single-photon emission computed tomography (SPECT) have shown that PET has a higher diagnostic accuracy. Beyond improved diagnostic performance, the quantitative flow measurements provided by PET represent an important advance in nuclear cardiology. The radiopharmaceuticals [ 15 O]H 2 O and [ 13 N]NH 3 have been applied for the noninvasive determination of regional coronary reserve. Quantification of blood flow based on tracer kinetic modeling yields blood flow values in close agreement with determinations provided by invasive procedures. The noninvasive quantification of blood flow provides a useful research and clinical tool for the objective assessment of therapeutic interventions as well as pathophysiologic alterations of regional myocardial blood flow in various cardiac diseases.