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N Nguyen

Publications and source records attributed to N Nguyen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Reproducibility of polar map generation and assessment of defect severity and extent assessment in myocardial perfusion imaging using positron emission tomography.

The purpose of this study was to determine the reliability of new software developed for the analysis of cardiac tomographic data. The algorithm delineates the long axis and defines the basal plane and subsequently generates polar maps to quantitatively and reproducibly assess the size and severity of perfusion defects. The developed technique requires an initial manual estimate of the left ventricular long axis and calculates the volumetric maximum myocardial activity distribution. This surface is used to map three-dimensional tracer accumulation onto a two-dimensional representation (polar map), which is the basis for further processing. The spatial information is used to compute geometrical and mechanical properties of a solid model of the left ventricle including the left heart chamber. A new estimate of the axis is determined from this model, and the previously outlined procedure is repeated together with an automated definition of the valve plane until differences between the polar maps can be neglected. This quantitative analysis software was validated in phantom studies with defects of known masses and in ten data sets from normals and patients with coronary artery disease of various severity. We investigated the reproducibility of the maps with the introduction of a similarity criterion where the ratio of two corresponding polar map elements lies within a 10% interval. The maps were also used to measure intra-and interobserver variability in respect of defect size and severity. In the phantom studies, it was possible to reliably assess mass information over a wide range of defects from 5 to 60 g (slope: 1.02, offset -0.68, r = 0.972). Patient studies revealed a statistically significant increase in the reproducibility of the automatic technique compared with the manual approach: 54%+/-19% (manual) compared with 88%+/-9% (automatic) for observer 1 and 61%+/-20% vs 82%+/-5% for observer 2, respectively. The intervariability analysis showed a significant improvement from 59%+/-14% to 83%+/-7% in similar polar map elements and a significantly improved correlation in the calculation of severity (from r = 0.908 to 0.989) and extent (from r = 0.963 to r = 0.992) of the perfusion defects when the automated procedure was applied. It is concluded that, assuming a constant wall thickness and tissue density, absolute defect mass can be reliably estimated. Furthermore, the proposed software demonstrates a significant improvement in the generation of volumetric polar maps for the quantitative assessment of perfusion defects.

Algorithms↗
PubMed1998

Neuromuscular blocking N,N'-polymethylene bistropanium, bis 3alpha-hydroxytropanium and bis 3-oxotropanium compounds.

To explore the role of ester groups in the neuromuscular blocking (NMB) property of various quaternary ammonium tropinesters, we have synthesized and pharmacologically evaluated twenty bisquaternary ammonium derivatives where two tropane (I), 3alpha-hydroxytropane (II), or 3-oxotropane (III) moieties were connected on their nitrogen atoms with a polymethylene chain of C3-C12 length. The rank order of potency of these agents in the rat (evoked EMG responses of the ant. tibial muscle) was: I, II, and III. Most potent were the longer chain (e.g. C10-C12) compounds of series I, yet they were inferior to bisquaternary ammonium tropinester derivatives (e.g. N,N'-polymethylene bisquaternary tropinesters, or bisquaternary derivatives of dicarboxylic acid tropinesters). Although some of the agents (series I and II) showed a rapid onset and short duration of action-profile, they also exhibited cardiovascular side effects (e.g. cardiac vagal block and blood pressure changes). In the design of new NMB agents of rapid onset and short duration of action the presence of different ester groups in addition to an azabicyclo ring system (e.g. tropane), seems to be essential.

Animals↗
PubMed1998

Polymorphic expression of the UDP-glucuronosyltransferase UGT1A gene locus in human gastric epithelium.

The human UDP-glucuronosyltransferase (UGT) 1A (UGT1A) locus is regulated in a tissue specific fashion in liver and extrahepatic tissues. Three extrahepatic UGT1A proteins, UGT1A7, UGT1A8, and UGT1A10, have been discovered and are believed to contribute to the diversity of extrahepatic glucuronidation. UGTs eliminate by glucuronidation a broad variety of endobiotic and xenobiotic substrates, which include bilirubin, therapeutic drugs, and carcinogens. Human gastric mucosa represents a primary location of tissue contact with dietary constituents, pharmaceutical drugs, and environmental carcinogens. To study the role and regulation of UGT1A gene products in stomach UGT1A mRNA expression and UGT catalytic activities were investigated in a panel of 14 normal gastric mucosa/adenocarcinoma sample pairs. UGT1A mRNA levels were differentially regulated in stomach, a feature not found in hepatic tissue. Normal gastric epithelium consistently expressed extrahepatic UGT1A7 and UGT1A10. However, polymorphic expression of UGT1A1 (29%), UGT1A3 (21%), and UGT1A6 (36%) was detected. Polymorphic UGT1A regulation was confirmed in adenocarcinoma samples with the additional observation of differential down-regulation of UGT1A1, UGT1A3, UGT1A6, and UGT1A10 and up-regulation of UGT1A7 mRNA. The polymorphic UGT1A regulation in stomach contrasts the homogeneous regulation of UGT1A gene products in human liver. Activity assays demonstrated 2- to 4-fold interindividual differences in UGT activity and qualitative differences between individuals. The polymorphic regulation of UGT1A gene products in gastric tissue may be the biological basis that determines interindividual differences in extrahepatic microsomal drug metabolism.

Adenocarcinoma↗
PubMed1997

Increased sarcolemmal glucose transporter abundance in myocardial ischemia.

Many clinical and laboratory studies suggest that an increase in glucose uptake and metabolism by ischemic myocardium helps protect myocardial cells from irreversible injury. We have examined whether increased sarcolemmal abundance of cardiomyocyte glucose transporters plays a role in this adaptive response. We have shown that acute myocardial ischemia in perfused rat hearts results in increased sarcolemmal abundance of the major glucose transporter, GLUT4, by causing translocation of GLUT4 molecules from an intracellular compartment to the sarcolemma. In nonischemic control hearts only 18 +/- 2.8% of GLUT4 molecules were on the sarcolemma whereas in ischemic hearts this increased to 41 +/- 9.3%. Insulin also caused translocation of GLUT4 molecules to the sarcolemma, and resulted in 61 +/- 2.6% of GLUT4 molecules on the sarcolemma. The combination of ischemia and insulin did not result in additive increases in sarcolemmal GLUT4 abundance. In more persistent or chronic ischemia, the other major myocardial glucose transporter, GLUT1, appears to play an important role. The mRNA for this transporter, which is constitutively expressed on cardiomyocyte sarcolemma, was increased 2.0-fold in regions of hibernating myocardium in humans with coronary heart disease as well as in persistently hypoxic rat neonatal cardiomyocytes in primary culture. In neither of these conditions was GLUT4 mRNA expression increased. Thus, acute myocardial ischemia increases sarcolemmal glucose transporter abundance mainly by translocating previously synthesized GLUT4 molecules from an intracellular compartment, whereas more chronic ischemia also increases GLUT1 abundance via enhanced mRNA expression. Increased GLUT1 and GLUT4 abundance may participate in the augmented glucose uptake of ischemic myocardium and therefore may help protect ischemic myocardium from irreversible injury.

Animals↗
PubMed1997

Differential immune recognition of LCMV nucleoprotein and glycoprotein in transgenic mice expressing LCMV cDNA genes.

We have generated doubly transgenic (DT) mice that independently express cDNA genes for the nucleocapsid protein (NP) and the surface glycoproteins (GP) of lymphocytic choriomeningitis virus (LCMV). By RT-PCR, transcription of both transgenes was detected at low levels in brain and kidney but was not observed in the thymus. Additionally, transcription of the GP transgene was observed in the spleen. Following challenge with exogenous LCMV, an anti-NP CTL response was induced in LCMV-infected DT mice, suggesting that nonresponsiveness to NP had not been established. In contrast, LCMV- infected DT mice were nonresponsive to GP and failed to mount any CTL response against GP, either at Day 7 or Day 30 postinfection or following expansion of splenocyte populations in vitro. A significant number (33%) of adult DT mice survived intracerebral infection with LCMV, suggesting that virus-induced immunopathology in the central nervous system can be diminished by combined expression of the transgenes whereas no protective effect was conferred on singly transgenic mice, expressing NP or GP alone. The DT mice therefore create a novel host genetic background for comparative studies of the anti-LCMV immune responses relative to parental C57Bl/6 mice.

Animals↗
PubMed1997

Production and purification of novel secreted human proteins.

Our objective during the last year was to produce and purify 50-80 novel, secreted human proteins identified via high throughput cDNA sequencing and computer analysis. We chose the baculovirus expression vector system in order to obtain secreted, correctly folded, bioactive proteins. Recombinant (re-)baculoviruses (BV) were plaque purified, and pulse-labeling was used to verify the synthesis and secretion of the re-proteins. N-terminal microsequencing was performed to simultaneously confirm the identity of the protein(s) as well as the signal peptide (SP) cleavage site(s). Following sequence confirmation, the proteins were purified to homogeneity and functional assays carried out to determine potential therapeutic applications. We identified proteins with antiviral activity, several novel growth factors, proteins influencing the differentiation of specific cell types, novel proteases and protease inhibitors among others. Certain proteins were expressed both in insect cells and in CHO stable cell lines. In the cases analyzed, we found that the same SP cleavage site was utilized in the two expression systems. Significant differences were observed in the carbohydrate moieties attached to the proteins, though no effects on the biological activity due to these differences have been demonstrated. The BV system has served as a viable alternative for the high throughput, high fidelity expression of many novel secreted human genes. To date, more than 75 new genes have been expressed, and the re-proteins purified. This expression system combines many favorable traits including relative speed, moderate cost but perhaps most importantly, the production of biologically active proteins.

Baculoviridae↗
PubMed1997

Cystatin E is a novel human cysteine proteinase inhibitor with structural resemblance to family 2 cystatins.

A new member of the human cystatin superfamily, called cystatin E, has been found by expressed sequence tag (EST) sequencing in amniotic cell and fetal skin epithelial cell cDNA libraries. The sequence of a full-length amniotic cell cDNA clone contained an open reading frame encoding a putative 28-residue signal peptide and a mature protein of 121 amino acids, including four cysteine residues and motifs of importance for the inhibitory activity of Family 2 cystatins like cystatin C. Recombinant cystatin E was produced in a baculovirus expression system and isolated. An antiserum against the recombinant protein could be used for affinity purification of cystatin E from human urine, as confirmed by N-terminal sequencing. The mature recombinant protein processed by insect cells started at amino acid 4 (cystatin C numbering), and displayed reversible inhibition of papain and cathepsin B (Ki values of 0.39 and 32 nM, respectively), in competition with substrate. Cystatin E is thus a functional cysteine proteinase inhibitor despite relatively low amino acid sequence similarities with human cystatins (26-34% identity with sequences for the Family 2 cystatins C, D, S, SN, and SA; <30% with the Family 1 cystatins, A and B, and domains 2 and 3 of the Family 3 cystatin, kininogen). Unlike other human low Mr cystatins, cystatin E is a glycoprotein, carrying an N-linked carbohydrate chain at position 108. Northern blot analysis revealed that the cystatin E gene is expressed in most human tissues, with the highest mRNA amounts found in uterus and liver. A strikingly high incidence of cystatin E clones in cDNA libraries from fetal skin epithelium and amniotic membrane cells (>0.5% of clones sequenced) indicates a protective role of cystatin E during fetal development.

Amino Acid Sequence↗
PubMed1997

Replacement of pre-T cell receptor signaling functions by the CD4 coreceptor.

An important checkpoint in early thymocyte development ensures that only thymocytes with an in-frame T cell receptor for antigen beta (TCR-beta) gene rearrangement will continue to mature. Proper assembly of the TCR-beta chain into the pre-TCR complex delivers signals through the src-family protein tyrosine kinase p56lck that stimulate thymocyte proliferation and differentiation to the CD4+CD8+ stage. However, the biochemical mechanisms governing p56lck activation remain poorly understood. In more mature thymocytes, p56lck is associated with the cytoplasmic domain of the TCR coreceptors CD4 and CD8, and cross-linking of CD4 leads to p56lck activation. To study the effect of synchronously inducing p56lck activation in immature CD4-CD8- thymocytes, we generated mice expressing a CD4 transgene in Rag2-/- thymocytes. Remarkably, without further experimental manipulation, the CD4 transgene drives maturation of Rag2-/- thymocytes in vivo. We show that this process is dependent upon the ability of the CD4 transgene to bind Lck and on the expression of MHC class II molecules. Together these results indicate that binding of MHC class II molecules to CD4 can deliver a biologically relevant, Lck-dependent activation signal to thymocytes in the absence of the TCR-alpha or -beta chain.

Animals↗
PubMed1997

Persistent myocardial ischemia increases GLUT1 glucose transporter expression in both ischemic and non-ischemic heart regions.

Persistently ischemic myocardium exhibits increased glucose uptake which may contribute to the preservation of myocardial function and viability. Little is known about the specific molecular events which are responsible for this increase in uptake. Therefore, we investigated whether myocardial ischemia induces the gene expression of the major cardiac facilitative glucose transporters, GLUT4 and GLUT1. We determined the expression of myocardial glucose transporter mRNAs and polypeptides after 6 h of regional ischemia in a dog model by semi-quantitative Northern blotting and immunoblotting. GLUT1 but not GLUT4 expression was significantly increased in both ischemic and non-ischemic regions from the experimental hearts when compared to surgical control and normal hearts. GLUT1 mRNA expression was increased 3.4-fold and GLUT1 polypeptide expression was increased 1.7-fold in ischemic hearts when compared to normal or surgical-control hearts. There were no significant regional differences in GLUT1 expression in either normal or ischemic hearts. However, there was a tendency for GLUT1 mRNA expression to be highest in the non-ischemic regions from the 6-h ischemia hearts. These findings suggest that myocardial ischemia induces a factor or factors which stimulate GLUT1 expression in non-ischemic as well as ischemic myocardial regions. Increased GLUT1 expression may play a role in augmenting glucose uptake during ischemia.

Animals↗
PubMed1997

Effects of wortmannin on insulin- and ischemia-induced stimulation of GLUT4 translocation and FDG uptake in perfused rat hearts.

OBJECTIVE: Myocardial glucose transport is enhanced by hormonal and other stimuli such as ischemia and hypoxia which induce glucose transporter 4 (GLUT4) translocation. Whether insulin and ischemia share a common signaling mechanism is not yet known. This study investigated whether phosphatidylinositol 3-kinase (PI3K), a signaling intermediate of the insulin-responsible pathway, also participates in the ischemia-induced stimulation of glucose. METHODS: Isolated Langendorff-perfused Sprague-Dawley rat hearts were subjected to 100 nmol/l insulin or 15 min of no-flow ischemia with/without 1 mumol/l wortmannin, an inhibitor of PI3K. After perfusion, relative subcellular glucose transporter GLUT4 distribution was assessed by membrane fractionation and immunoblotting and compared to controls. Uptake kinetics of the glucose analog [18F]fluoro-deoxyglucose (FDG) were also studied during perfusion of rat hearts. RESULTS: GLUT4 translocation to the plasma membrane (PM) was increased by insulin 1.8-fold and by ischemia 2.4-fold (P < 0.05). FDG uptake was increased by insulin 6.0-fold and by ischemia 6.2-fold (P < 0.05). Wortmannin 1 mumol/l inhibited insulin-mediated translocation of GLUT4 and increase in FDG uptake completely. However, it did not show any effect on ischemia-stimulated GLUT4 translocation or on ischemia-induced increase in FDG utilization. A significant correlation was found between relative GLUT4 translocation and FDG uptake in hearts of the insulin series (r = 0.9, P < 0.05) and of the ischemia series (r = 0.8, P < 0.05). CONCLUSIONS: Our results demonstrate that wortmannin did not inhibit ischemia-induced stimulation of myocardial glucose transport, supporting the hypothesis of different signaling pathways for ischemia and insulin.

Androstadienes↗
PubMed1997

Minimally invasive surgical staging is superior to endoscopic ultrasound in detecting lymph node metastases in esophageal cancer.

OBJECTIVE: Endoscopic ultrasonography is frequently used to locally stage esophageal cancer, but few studies exist to validate its accuracy for lymph node metastases. Our objective was to compare endoscopic ultrasonography with video-assisted thoracoscopic and laparoscopic staging in evaluating lymph node metastases in esophageal cancer. METHODS: Twenty-six patients with potentially resectable esophageal cancer were identified by conventional imaging. Endoscopic ultrasonography was performed followed by laparoscopic and thoracoscopic staging, and locoregional staging was compared. RESULTS: In eight patients endoscopic ultrasonography indicated N0 disease, but laparoscopy and thoracoscopy documented N1 disease in six. In five of 26 (19%) obstruction prevented endoscopic ultrasonography; three had N1 by laparoscopy and thoracoscopy. Thirteen patients had N1 disease according to endoscopic ultrasonography, and 12 of 13 (92%) had N1 disease by laparoscopy and thoracoscopy. The sensitivity and specificity of endoscopic ultrasonography for nodal evaluation were 65% and 66%, respectively. Sensitivity decreased to 44% for lymph node metastases less than 1 cm. No instances of T4 disease were found by surgical staging when endoscopic ultrasonography indicated T3 disease. Endoscopic ultrasonography revealed no distant metastases in any patient, but in four of 26 (15%) laparoscopy identified liver metastases. CONCLUSIONS: The accuracy of endoscopic ultrasonography in the diagnosis of lymph node metastases in esophageal cancer was 65% and only 44% for lymph node metastases less than 1 cm diameter. Laparoscopy and thoracoscopy improved the accuracy of staging lymph node metastases in esophageal cancer and had the advantage of evaluating the thoracic and abdominal cavities for metastases.

Adenocarcinoma↗
PubMed1997

Clinical experience of trabeculotomy for the surgical treatment of aniridic glaucoma.

OBJECTIVE: The purpose of this study is to determine the efficacy of initial trabeculotomy in the patient with aniridic glaucoma. DESIGN: Clinical charts were reviewed. PARTICIPANTS: Twenty-nine eyes of 16 patients with aniridia were studied. INTERVENTION: Glaucoma surgery was performed. As an initial procedure, trabeculotomy was performed in 12 eyes, other surgery was performed in 17 eyes (trabeculectomy, 5; goniotomy, 5; other, 7). MAIN OUTCOME MEASURES: Success was defined as an intraocular pressure (IOP) of 21 mmHg or lower, and no further surgery was performed. RESULTS: Ten (83%) of 12 eyes obtained IOP control after first (6 eyes) or second (4 eyes) trabeculotomy with a mean follow-up period of 9.5 years. Five eyes maintained visual acuity of 20/40 to 20/200. No serious complications were found after trabeculotomy. Three (18%) of 17 eyes were controlled with the first glaucoma surgery other than trabeculotomy (goniotomy, trabeculectomy, trabeculectomy combined with trabeculotomy, and Molteno implant). Good IOP control was obtained in 8 (47%) of 17 eyes after several surgeries with a mean follow-up period of 10.4 years. Four of 17 eyes became phthisical. CONCLUSION: This study suggests that trabeculotomy is the preferred initial operation for uncontrolled glaucoma with aniridia.

Adolescent↗
PubMed1997

Endoscopic diode laser cyclophotocoagulation with a limbal approach.

BACKGROUND AND OBJECTIVE: Endoscopic diode laser cyclophotocoagulation with a limbal approach was reviewed retrospectively. The delivery system and procedure used as well as the role of this procedure in the management of glaucoma are discussed. PATIENTS AND METHODS: An 810-nm pulsed continuous-wave diode laser capable of 1.2-W output was used. The maximum treatment area is 7 to 8 clock hours with a single limbal incision. Generally, 800 mW were used for less than 1 second, for a total of 0.8 J per treatment. RESULTS: Eight eyes of 6 patients were treated. The mean follow-up time for each procedure was 3.2 months (range 1 to 8 months) and for each eye was 5.1 months (range 2 to 8 months). Pre- and postoperative intraocular pressures were determined. Postoperative inflammation was the most common complication. CONCLUSION: One reason for the failure of transscleral cyclophotocoagulation, particularly in congenital glaucoma, may be displacement of the ciliary processes. This displacement does not permit the indirect treatment to reach the appropriate area. Because endoscopic laser cyclophotocoagulation allows direct visualization, treatment can be accurately applied to individual ciliary processes.

Adult↗
PubMed1997

Baculovirus-directed expression of rabbit UDP-glucuronosyltransferases in Spodoptera frugiperda cells.

The rabbit liver UDP-glucuronosyltransferase (UGT) cDNAs that encode the 4-hydroxybiphenyl UGT2B13 and 4-nitrophenol UGT1A6 have been cloned into baculovirus. Spodoptera frugiperda (SF-9) cells infected with the UGT recombinant baculovirus produced significant amounts of protein, which was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot analysis, and pulse chase with 35S-amino acids. The expression of the UGT proteins in SF-9 cells were detected at approximately 24 hr postinfection, with maximal levels of protein seen at 48 hr. Immunoprecipitation of newly synthesized 35S-labeled proteins demonstrated that the maximal rate of protein synthesis in SF-9 cells infected with the UGT baculovirus occur at 48 hr postinfection, although the proteins are abundant in the cells for up to 96 hr. When compared with the expression levels of the same cDNAs through transient transfection into COS-1 cells, the insect-derived UGT proteins showed nearly 50- to 100-fold greater protein accumulation. Although kinetic analysis demonstrated that turnover rate of the SF-9-expressed proteins were greater than their counterparts in COS-1 cells, K(M) values for UGT1A6 and UGT2B13 in SF-9 and COS-1 cells were similar. Overall, SF-9 cells seem to serve as an efficient expression system for the production of the mammalian UGTs.

Animals↗
PubMed1996

IL-4 is protective against development of toxoplasmic encephalitis.

IFN-gamma is critical for prevention of development of toxoplasmic encephalitis (TE). Since IL-4 down-regulates production of IFN-gamma, we examined its role in the pathogenesis of TE in IL-4-targeted mutant (IL-4-/-) mice. IL-4-/- mice all died from 6 to 20 wk after peroral infection with cysts of the ME49 strain of Toxoplasma gondii; control mice survived. At 4 and 8 wk after infection, significantly greater numbers of T. gondii cysts and foci of acute inflammation, and greater amounts of tachyzoite-specific mRNA (by reverse-transcriptase PCR) were in brains of IL-4-/- mice than controls. Toxoplasma IgG2b and IgG3 Ab levels were slightly but significantly higher in sera of IL-4-/- than control mice, whereas IgM and IgG2a levels did not differ between these mice. Toxoplasma IgG1 and IgE Abs were not detected in sera of either strain. Amounts of IFN-gamma, TNF-alpha, IL-6, and IL-10 mRNA detected by reverse-transcriptase PCR did not differ between brains of infected IL-4-/- and controls, although brains of the former mice had greater numbers of inflammatory mononuclear cell infiltrates. IL-4 mRNA was detected only in infected control mice. Spleen cells of control mice at 8 wk after infection produced significantly greater amounts of IFN-gamma following stimulation in vitro with soluble T. gondii Ags than did those from IL-4-/- mice. These results indicate that IL-4 is protective against development of TE by preventing formation of T. gondii cysts and proliferation of tachyzoites in the brain. The impaired ability of IL-4-/- mice in the late stage of T. gondii infection to produce IFN-gamma most likely contributes to their susceptibility for development of severe TE.

Animals↗
PubMed1996

Corticotropin-releasing hormone challenge in prepubertal major depression.

This study investigates cortisol and ACTH (corticotropin) responses to an infusion of human CRH (corticotropin-releasing hormone) in prepubertal children with major depressive disorder (MDD). Following a period of 24 hours of adaptation to the laboratory environment with an intravenous catheter in place, 34 children with MDD and 22 healthy controls received 1 microgram/kg of human CRH at 5:00 PM. Blood samples for cortisol and ACTH were measured at baseline and post-CRH. Overall, there were no significant differences between the MDD and the normal controls in baseline or post CRH stimulation values of either cortisol or ACTH. Melancholic (n = 4) patients had significantly higher baseline cortisol levels than nonmelancholic (n = 24) patients. Compared with the outpatients and the nonmelancholics, the inpatients (n = 10) and the melancholics showed significantly lower total ACTH secretion (effect size: 0.9 and 1.4, respectively) after CRH infusion. These results are consistent with a broad literature suggesting that the HPA axis abnormalities occur less frequently in early-onset depression than reported in adult studies. The pattern of results in the subgroups of inpatients and in melancholic children, however, raise questions about possible continuities with adult studies.

Adolescent↗
PubMed1996

Quantitative evaluation of manganese-52m as a myocardial perfusion tracer in pigs using positron emission tomography.

There is a need for a quantitative myocardial perfusion agent that does not require an on-site cyclotron. Early studies with manganese demonstrated that this trace metal is of potential use for myocardial imaging. 52mMn can be produced in a 52Fe-52mMn generator and is suitable for positron emission tomographic (PET) imaging. The purpose of this study was to evaluate 52mMn with regard to its potential to quantitatively assess myocardial perfusion. Dynamic PET imaging was performed in six pigs with various doses of dipyridamole to increase blood flow. Retention (R) and model-based K1 values were correlated with microsphere blood flow. The models consisted of one (K1, k2) and two (K1, k2, k3) tissue compartments. Anterior, lateral and septal regions showed a good myocardium-to-background ratio; the evaluation of the inferior wall was impaired by high liver uptake. Linear regression yielded the following equations: K1=1.152 flow+0.059 (r=0.92), R=0.069 flow+0.034 (r=0.84). Based on these regressions, K1 increased 2.7-fold and R 2.6-fold in the examined flow range of 0.5-2 ml/min/g (fourfold increase), demonstrating an underestimation of higher flow rates by both measures. It is concluded that 52mMn allows the qualitative assessment of myocardial perfusion but does not meet the requirements of a quantitative myocardial perfusion agent.

Animals↗