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PubMed1973

Improved hemagglutination inhibition assay for mammary tumor virus antigen.

It is our experience that the use of sheep red blood cells pretreated with formaldehyde and pyruvaldehyde before sensitizing with viral antigen yields results that are comparable to that obtained by using the tannic acid method. The double aldehyde method provides the added advantage of being useful for assaying the viral antigen content in substances which contain high levels of interfering substances which would preclude the use of other assay methods.

Aldehydes↗

PubMed1990

Assessment of regional myocardial and renal blood flow with copper-PTSM and positron emission tomography.

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.

Animals↗

PubMed1993

Quantification of regional myocardial perfusion with generator-produced 62Cu-PTSM and positron emission tomography.

BACKGROUND: Noninvasive assessment of regional myocardial perfusion at rest and after stress is important for the objective evaluation of the effects of coronary artery disease and its response to therapy. Centers that do not have cyclotrons rely on generator-produced radioisotopes for assessment of regional myocardial perfusion with positron emission tomography (PET). The aim of the present study was to develop and implement an approach to quantify regional myocardial perfusion using copper(II) pyruvaldehyde bis-(N4-thiosemicarbazone) (PTSM) labeled with the generator-produced, positron-emitting radionuclide 62Cu (t1/2 = 9.7 minutes). METHODS AND RESULTS: Regional perfusion was estimated from dynamic PET scans after intravenous administration of 62Cu-PTSM in 21 studies in 13 intact dogs evaluated over a wide range of myocardial flow values. In 15 interventions in nine dogs, regional perfusion was also estimated with H2(15)O. Regional perfusion with 62Cu-PTSM was estimated from dynamic blood and tissue time-activity curves, along with the model parameter k1 (forward rate of transport) and the PET parameter FBM (fraction of blood pool activity observed in tissue), using a two-compartment kinetic model. Arterial blood activity was corrected for red blood cell-associated 62Cu. In 44 comparisons, estimates of regional perfusion with 62Cu-PTSM correlated well with estimates obtained with concomitantly administered radiolabeled microspheres (y = 0.90x +/- 0.15, r = 0.95, p < 0.05) over a flow range from 0.23 to 6.14 ml/g per minute. In five healthy human volunteers evaluated at rest with H2(15)O and 62Cu-PTSM, regional perfusion estimated with 62Cu-PTSM was not significantly different from that obtained with H2(15)O (1.05 +/- 0.36 versus 0.96 +/- 0.28 ml/g per minute). 62Cu-PTSM provided high-quality images of the heart. CONCLUSIONS: The results of this study demonstrate that quantification of regional myocardial perfusion is feasible using generator-produced 62Cu-PTSM. Since 62Cu-PTSM can be used to estimate perfusion in the brain, kidney, and tumors as well as in the heart, it is an attractive tracer for centers that rely on generator-produced tracers for the evaluation of perfusion with PET.

Animals↗

PubMed2005

Suppressive effect of trehalose on acrylamide formation from asparagine and reducing saccharides.

The influence of saccharides on the formation of acrylamide (AcA) was investigated. The reducing saccharides reacted with asaparagine to form AcA, but the non-reducing saccharides, except sucrose, gave no AcA. AcA formation from a mixture containing glucose and asaparagaine was suppressed by the non-reducing saccharides, especially trehalose (76% suppression) and neotrehalose (75% suppression). Glucose is heat-degraded into pyruvaldehyde and 5-hydroxymethyl-2-furfural in the water system. The degradation products react with asparagines to generate AcA. Trehalose appears to inhibit not only the formation of these intermediates and asparagines for AcA, but also the AcA formation from these intermediates.

Acrylamide↗

PubMed2007

Effects of high pressure treatment on volatile profile during ripening of ewe milk cheese.

The effect of high-pressure treatment on the volatile profile of ewe milk cheeses was investigated. Cheeses were submitted to 200, 300, 400 and 500 MPa at 2 stages of ripening (after 1 and 15 d of manufacturing) and volatile compounds were assayed at 15 and 60 d of ripening. High-pressure treatment altered the balance of volatile profile of cheeses, limiting the formation of acids, alcohols, ketones, aldehydes, and sulfur compounds and enhancing the formation of 2,3-butanedione. In general, cheeses pressurized at 15 d of ripening were more similar to untreated cheeses than those treated at 1 d. Cheeses treated at 300 MPa after 1 d of manufacturing were characterized by higher levels of free amino acids, ethanol, ethyl esters, and branched-chain aldehydes, whereas cheeses treated at 500 MPa after 1 d of manufacturing had lower microbial populations, showed the highest abundance of 2,3-butanedione, pyruvaldehyde, and methyl ketones, and the lowest abundance of alcohols.

Animals↗

PubMed2000

Performance of a 62Zn/62Cu generator in clinical trials of PET perfusion agent 62Cu-PTSM.

UNLABELLED: The 62Zn/62Cu PET generator can be inexpensively produced and distributed from a single production site operating under typical good manufacturing practice guidelines. It therefore has the potential to greatly facilitate development of clinically practical PET. We report generator performance in a study in which 62Cu-pyruvaldehyde-bis(n4-methylthiosemicarbazone (PTSM) myocardial perfusion imaging is compared with 99mTc-sestamibi in the diagnosis of coronary artery disease. The 62Zn/62Cu generator is an improved version of a previously reported system that employs automated synthesis of 62Cu-PTSM. With this approach, the cumbersome step of 18C purification has been eliminated. METHODS: The 62Zn (9.3 h half-life) parent isotope is prepared by proton bombardment of natural copper at 33 MeV. A typical target irradiated with 37.5 microA/h is delivered by 12:00 PM on the day it is to be processed. Purified 62Zn obtained from the target is loaded onto the generator column in 2 mol/L HCl. The generator is eluted using an internal three-channel peristaltic pump, which delivers 2.25 mL eluant (1.8 mol/L NaCl, 0.2 mol/L HCl) through the generator column to elute the 62Cu in 40 s. The same pump simultaneously pumps an equal volume of buffer (0.4 mol/L NaOAc) and 1 mL ligand solution (2 ppm PTSM, 2% EtOH) passing it through a septum into a 35-cc syringe preloaded with 28 mL sterile water. This solution is thoroughly mixed by agitation of the syringe and injected as a bolus through a 0.2 microm filter. The generator is eluted twice before shipping, providing quality assurance samples, and shipped to the clinical site by overnight delivery. Complete quality assurance testing is performed the evening before the generator reaches the clinical site. RESULTS: A total of 34 generators have been produced and shipped to 2 clinical sites for a phase III Food and Drug Administration study. The load activity on the generators at 8:00 AM the day of clinical use was 1.7+/-0.2 GBq (46.7+/-5.6 mCi), and yield was 72%+/-16%. Breakthrough of 62Zn was undetectable by high-purity germanium spectroscopy for all units. Radiochemical purity was 95.4%+/-2.4%. Volume delivered, pH, sterility, and bacterial endotoxin tests yielded passing results on all generators. The entire process of generator production, from target receipt to generator shipment, took less than 6 h and cost approximately $1000, including shipping charges and cyclotron cost. A total of 68 patients were injected with 2 62Cu-PTSM doses, with a mean injected activity of 0.8+/-0.2 GBq (20.5+/-5.3 mCi) with no adverse side effects. CONCLUSION: Results of this work confirm that the 62Zn/62Cu generator is an easily produced, transportable, and inexpensive source of PET radiopharmaceuticals, which can expand the field of clinical PET imaging by providing radiopharmaceuticals to sites not associated with cyclotrons.

Clinical Trials, Phase III as Topic↗

PubMed2003

Enhancing targeted radiotherapy by copper(II)diacetyl- bis(N4-methylthiosemicarbazone) using 2-deoxy-D-glucose.

Most cancer deaths are a consequence of resistance to conventional chemotherapy and radiation therapy. This may be attributable to unique phenotypic characteristics of solid tumors. We have exploited two well-described characteristics of solid tumors commonly associated with treatment failure, high glucose use and hypoxia, to design a unique therapy based on the selective accumulation of two cytotoxic compounds, 2-deoxyglucose (2-DG) and copper(II)diacetyl-bis(N(4)-methylthiosemicarbazone) ((64)Cu-ATSM). (64)Cu-ATSM localizes to hypoxic regions of tumors and has been used for administering a high local dose of radiation therapy after uptake by cells. 2-DG, a glucose analog, selectively accumulates in cancer cells and interferes with energy metabolism, resulting in cancer cell death. 2-DG has been shown to potentiate the cytotoxic effect of ionizing radiation and certain chemotherapeutic agents. We have tested the effect of 2-DG on tumor response when combined with (64)Cu-ATSM in a mouse breast tumor model using the highly aggressive mouse mammary carcinoma cell line EMT-6. 2-DG administered up to 2 mg/g of body weight daily resulted in no weight loss or systemic symptoms. EMT-6 mammary tumors had similar uptake of [(18)F]fluoro-2-deoxyglucose before and after 2 weeks of 2-DG treatment as determined by microPET imaging, indicating that resistance to 2-DG uptake does not develop. Pretreatment of tumor-bearing mice with 2-DG resulted in increased uptake of (64)Cu-ATSM by tumors compared with nontreated mice. This effect was not observed with the nonhypoxia-specific agent copper(II)pyruvaldehyde-bis(N(4)-methylthiosemicarbazone. When 2-DG was combined with a single dose of (64)Cu-ATSM (2 mCi), tumor growth was inhibited approximately 60% compared with untreated mice, and animals survived approximately 50% longer than untreated mice or animals treated with each agent alone (32 versus 20 days). The maximum effect on tumor growth and survival was observed when 2-DG was administered daily for the lifetime of the mouse. Our results indicate that 2-DG potentiates the effect of (64)Cu-ATSM on tumoricidal activity and animal survival. We hypothesize that 2-DG alters the metabolic state of the cell, leading to increased uptake of (64)Cu-ATSM by the tumor. This would result in a higher local dose of radiotherapy. The continued presence of 2-DG would then prevent the repair of damaged cells, leading to inhibition of tumor growth. Our data indicate that the strategy of combining tumor-specific cytotoxic agents that function by differing mechanisms can result in an effective, selective, tumor-specific cell death with minimal effect on the host.

Animals↗

PubMed1992

The kinetics of copper-62-PTSM in the normal human heart.

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.

Adenosine↗

PubMed2006

Stem cells: a regenerative pharmaceutical.

Stem cells (SC), found in both adult and fetal tissues, are self-renewing elements that can generate the various cell types in the body. There are 3 classes of SC: totipotent, multipotent, and pluripotent. The SC with a significant developmental potential are the embryonic stem (ES) cells, which are derived from the early stages of mammalian embryo. SC possess regenerative properties and this offers unprecedented opportunities for developing medical therapies for debilitating diseases. Hematopoietic SC have been used successfully in bone marrow transplants for over 40 years. Pluripotent SC offer renewable source of replacement of cells and tissues to treat a myriad of diseases. However there are limiting factors. Adult SC are rare and cannot multiply as the ES. Pluripotent SC have great therapeutic potential, but face technical challenges. A serious concern is the ethical issue since they are derived from human embryos or fetal tissue. Quite often SC have been targets of mutations and risk carcinogenesis. Various markers have been identified based on the uniqueness of SC receptors and in vivo tracking studies using nanocolloids and radioactive tracers have been performed. Though 111In-oxine has been used to image SC transplants, PET with a high spatial resolution would be ideal. Currently 2 agents are being studied, 18F-FDG and 64Cu-Pyruvaldehyde bi(N4-methylthiosemicarbazone). The following few pages bring forth the various limitations and summarize progress made in SC utilization so as to create awareness of SC research in ISORBE community and to foster strategy that ISORBE community can disseminate information and exchange knowledge on radio labeled SC.

Humans↗

PubMed1989

Kinetics of copper-PTSM in isolated hearts: a novel tracer for measuring blood flow with positron emission tomography.

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) ([Cu]PTSM) has shown potential as a flow tracer and can be labeled with the generator-produced positron emitting radionuclide 62Cu as well as with other copper radioisotopes. To define the myocardial handling of [Cu]PTSM, the externally detected single pass extraction and retention of [67Cu]PTSM was characterized after bolus administration in 12 isolated rabbit hearts perfused with erythrocyte-enriched modified Krebs-Henseleit buffer which permitted physiologic flow rates. The myocardial residual (extraction) fraction at control flow rates (approximately 1.5 ml/g/min) was 45 +/- 7(s.d.)% (n = 12), and was invariate with ischemia (flow = 0.15 ml/g/min, n = 4), hyperemia (flow = 3 ml/g/min, n = 4) or with hypoxia induced by perfusion at control flow rates with hypoxic buffer (n = 4) (residual fraction 45 +/- 20, 43 +/- 8, and 49 +/- 8%, respectively, p = N.S.). Once extracted, the tracer was retained with a biologic t1/2 of greater than 3600 min in all groups. The high single-pass extraction, which is not influenced by flow, and the prolonged retention of this tracer under diverse conditions indicate that [Cu]PTSM could be a useful tracer for measuring blood flow with positron emission tomography.

Animals↗

PubMed1979

Formaldehyde dehydrogenase from Pseudomonas putida. Purification and some properties.

Formaldehyde dehydrogenase was isolated and purified in an overall yield of 12% from cell-free extract of Pseudomonas putida C-83 by chromatographies on columns of DEAE-cellulose, DEAE-Sephadex A-50, and hydroxyapatite. The purified enzyme was homogeneous as judged by disc gel electrophoresis and was most active at pH 7.8 using formaldehyde as a substrate. The enzyme was also active toward acetaldehyde, propionaldehyde, glyoxal, and pyruvaldehyde, though the reaction rates were low. The enzyme was NAD+-linked but did not require the external addition of glutathione, in contrast with the usual formaldehyde dehydrogenase from liver mitochondria, baker's yeast, and some bacteria. The enzyme was markedly inhibited by Ni2+, Pd2+, Hg2+, p-chloromercuribenzoate, and phenylmethanesulfonyl fluoride. The molecular weight of the enzyme was estimated to be 150,000 by the gel filtration method, and analysis by SDS-polyacrylamide gel electrophoresis indicated that the enzyme was composed of two subunit monomers. Kinetic analysis gave Km values of 67 microM for formaldehyde and 56 microM for NAD+, and suggested that the reaction proceeds by a "Ping-pong" mechanism. The enzyme catalyzed the oxidation of formaldehyde accompanied by the stoichiometric reduction of NAD+, but no reverse reaction was observed.

Aldehyde Oxidoreductases↗

PubMedDate not supplied

Detection of duck plague virus by reverse passive hemagglutination test.

A reverse passive hemagglutination (RPHA) test was developed to detect duck plague virus (DPV). The technique used sheep erythrocytes stabilized with formaldehyde and pyruvaldehyde and coated with immunoglobulin G (IgG) containing anti-DPV antibody prepared from antiserum produced in sheep. Optimum coating of stabilized erythrocytes occurred at 25 C and pH 4.0 with a concentration of IgG of 20-40 micrograms/ml and a 90-min incubation period. The coated cells were stable for 40 days when stored at 4 C or for at least 4 months (the longest period tested) when frozen at -70 C or -196 C. The RPHA test was conducted at 25 C and read after 3 hours. The high specificity of the test is indicated by the absence of cross-reactions with heterologous virus strains, with specimens prepared from normal duck livers, and with normal chicken embryo chorioallantoic fluid, as well as by the inhibition of hemagglutination only with DPV antiserum. The RPHA test detected six strains of DPV in all virus-containing specimens as well as the immunofluorescence (IF) test did; however, conventional plaque assays (PA) failed to detect virus in five specimens that contained three non-plaque-forming strains of DPV. The mean quantity of DPV that could be detected in the RPHA test was 25 plaque-forming units or 65 fluorescent units per ml. Although the RPHA test was less sensitive than either the PA or the IF test, there was a positive correlation in the titers of DPV antigens between all three tests. The RPHA test is a rapid, simple procedure that is sufficiently sensitive for diagnostic detection of DPV in acute infections, especially in tissues of ducks dying of the disease.

Animals↗

PubMed1995

Species-dependent binding of copper(II) bis(thiosemicarbazone) radiopharmaceuticals to serum albumin.

UNLABELLED: Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)-copper(II) (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 62Cu-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 67Cu-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 67Cu-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 62Cu-PTSM behavior in humans. The 62Cu-ETS and 62Cu-n-PrTS complexes may be viable alternatives to 62Cu-PTSM for PET studies to evaluate quantitatively myocardial blood flow in humans.

Animals↗

PubMed1976

Oxidation of the carbanion intermediate of transaldolase by hexacyanoferrate (III).

The transaldolase-dihydroxyacetone carbanion intermediate formed in the reaction of transaldolase with its donor substrates fructose-6-P or sedoheptulose-7-P is susceptible to oxidation by hexacyanoferrate(III). The dihydroxyacetone moiety is oxidized to the corresponding 2-ketoaldehyde, i.e. hydroxy-pyruvaldehyde (CH2OH-CO-CHO). This oxidation product is, in contrast to dihydroxyacetone, readily released from the enzyme. In the presence of hexacyanoferrate(III) transaldolase thus functions as an efficient catalyst of the oxidative cleavage of its donor substrates fructose-6-P or sedoheptulose-7-P into hydroxypyruvaldehyde and glyceraldehyde-3-P or erythrose-4-P, respectively. Two moles of hexacyanoferrate(III) are reduced per mole of oxidatively cleaved donor substrate. The molecular activity for oxidative cleavage of fructose-6-P at a hexacyanoferrate(III) concentration of 0.5 mM is 0.65% of that for the normal transfer reaction with erythrose-4-P as the acceptor substrate. The present data emphasize the applicability of certain oxidants as trapping agents for enzymatic carbanion intermediates as proposed previously (Healy, M.J.,, and Christen, P. (1973) Biochemistry 12, 35-41).

Dihydroxyacetone↗

PubMed1994

Clinical application and quantitative evaluation of generator-produced copper-62-PTSM as a brain perfusion tracer for PET.

UNLABELLED: Copper-62-pyruvaldehyde bis(N4-methylthiosemicarbazone) copper II (62Cu-PTSM) has been proposed as a generator-produced positron-emitting tracer for perfusion imaging. To evaluate the characteristics of 62Cu-PTSM as a cerebral perfusion tracer, brain PET images of 62Cu-PTSM were compared with cerebral blood flow (CBF). METHODS: Following an intravenous injection of 62Cu-PTSM, a serial dynamic PET scan was performed for 10 min with arterial sampling in 10 subjects. CBF was measured by 15O-labeled water before the 62Cu-PTSM study. RESULTS: Dynamic PET scan with octanol-extracted arterial input function indicated the presence of significant back-diffusion of 62Cu-PTSM from the brain within 3 min after injection, followed by stable activity from 3 to 10 min. Comparison with 15O-water PET demonstrated less contrast between high- and low-flow regions in 62Cu-PTSM image and a nonlinear relationship of flow and 62Cu-PTSM uptake, which suggests the underestimation of CBF in high-flow regions due to the existence of back-diffusion. CONCLUSION: Although 62Cu-PTSM can be used widely for evaluation of brain perfusion with PET, kinetic analysis and correction may be needed to quantify regional CBF.

Adolescent↗

PubMed1994

Myocardial kinetics of potassium-38 in humans and comparison with copper-62-PTSM.

UNLABELLED: The aim of this study was to define the kinetics of 38K and its suitability to evaluate myocardial blood flow at rest and during pharmacological vasodilation in normal subjects. Potassium-38's kinetic characteristics were also compared to those of a 62Cu-pyruvaldehyde bis(n4-methyl-thio-semicarbazone) copper (II) (PTSM) flow tracer. METHODS: Potassium-38 and 62Cu-PTSM were injected at rest and after pharmacological vasodilation in six healthy volunteers. Dynamic PET acquisition was performed over 20 min and myocardial tracer retention calculated. Homogeneity of regional myocardial tracer distribution was also evaluated. RESULTS: High image quality of the heart was observed at rest and after dipyridamole with both tracers. Potassium-38 demonstrated prolonged myocardial retention with minimal lung and liver accumulation. In contrast to 38K, 62Cu-PTSM demonstrated high liver uptake which may hinder observation of the inferior wall of the myocardium. Copper-62-PTSM dipyridamole-to-rest retention ratio was 1.49. CONCLUSIONS: Potassium-38 and 62Cu-PTSM display suitable kinetics for the qualitative evaluation of blood flow and flow reserve in the human heart. Compared to 62Cu-PTSM, potassium-38, which does not show high liver uptake, may more accurately estimate blood flow in the inferior wall of the heart. However, accurate quantification of myocardial blood flow using 38K or 62Cu-PTSM retention appears to be limited to decreasing retention fraction at hyperhemic states.

Adult↗

PubMed1996

Regional myocardial perfusion assessed with generator-produced copper-62-PTSM and PET.

UNLABELLED: We have previously demonstrated that myocardial perfusion can be estimated accurately in experimental animals with the generator-produced positron-emitting tracer, 62Cu-pyruvaldehyde bis (N4-methylthio- semicarbazone)(62Cu-PTSM) and PET. This study evaluated the feasibility of quantifying regional myocardial blood flow using 62Cu-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 62Cu-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 H2(15)O. RESULTS: Contrast was high between myocardium and blood or lung with 62Cu-PTSM, resulting in high-quality myocardial images. Liver uptake was also high. At flows of up to 1.5 ml/g/min, flow estimated with 62Cu-PTSM correlated closely with estimates obtained with H2(15)O (y = 0.71x .21, n = 169 regional comparisons, r = 0.66, p < 0.55), but this relationship was not maintained at higher flows. CONCLUSION: The results demonstrate that quantification of myocardial perfusion with 62Cu-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.

Adult↗

PubMed1996

Generator-produced copper-62-PTSM as a myocardial PET perfusion tracer compared with nitrogen-13-ammonia.

UNLABELLED: The purpose of this study was to determine the suitability of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) for estimating myocardial blood flow (MBF) over a wide range of flow by comparison with 13N-ammonia (13NH3). METHODS: PET studies using 62Cu-PTSM and 13NH3 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 62Cu-PTSM studies and lower in the lateral wall in the 13NH3 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 62Cu-PTSM were nonlinearly proportional to the increase of those for 13NH3 (y = 1.1 x -0.21x2, 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 62Cu-PTSM was noted compared to that with 13NH3 at high flows (y = 31.8 + 0.63x, r = 0.76). CONCLUSION: These results suggest that the MBF estimates using 62Cu-PTSM in a low flow range may be as accurate as those with 13NH3. In a high flow range, however, the extraction fraction of 62Cu-PTSM is considered to be lower than that of 13NH3, and this may limit the estimation of MBF with 62Cu-PTSM after pharmacological vasodilatation.

Ammonia↗