L-(13N)-glutamate (4-8 mCi) was administered IV to 27 patients with coronary artery disease and to 12 control subjects. Quantitative whole body imaging of the 13N label was performed in 31 individuals at different time intervals following the injection. Initial uptake of the total myocardium was estimated to be 5.0 +/- 0.88% of the dose. Standardized areas of reduced size on the projection plane contained 2.38 +2- 0.41% of the total dose in control subjects and 2.67 +/- 0.49% in coronary patients. Subsequent imaging exhibited significant differences in the dynamic behavior of both groups: 13N activity loss within 10 min was 3.2 +/- 4.2% of the initial value in control subjects and 16.0 +/- 9.8% in coronary patients. In individual cases a high myocardial accumulation of the 13N label was observed in regions of reduced 201Tl uptake. The findings are explained by an augmented extraction efficiency in cases of flow reduction. Glutamate utilization may be involved in metabolic adaptations of the myocardium to chronic or repetitive ischemia and may be worthy of further investigation by positron emission tomography.
To study kinetics and principles of cellular uptake of '3N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of '3N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 370 C). Total extraction, 80 sec after the reaction start, was 786 ± 159 ,umol/ml cell volume. Cells destroyed by calcium overload were unable to extract 13N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. '3N-Ammonia uptake could also be reduced by 50 gM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 ,ug/ml 1-methionine sulfoximine, and by preincubation with 5 gtM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of 13N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of 13N-ammonia may not always provide a valid measurement of myocardial perfusion. Circulation 71, No. 2, 387-393, 1985. 13N-AMMONIA (13N),* a positron-emitting radionuclide, has been used as a marker of myocardial perfusion.' 8 Because cellular extraction of an ideal flow marker must be proportional to regional myocardial blood flow, extraction of such a marker should not be influenced by cell metabolism or cell membrane transport mechanisms. Since myocardial extraction fraction of '3N-ammonia can be significantly reduced when intracellular glutamine synthetase is inhibited,67 the usefulness of this compound as a flow marker has been questioned. This study provides additional data regarding the kinetics and possible role of the plasma membrane in myocardial '3N uptake and retention in isolated adult rat heart cells. Materials and methodsPreparation of myocardial single cells. Male Wistar rats 3 to 4 months old were heparinized and anesthetized by urethane (1.5 mg/g body weight, intraperitoneally). Hearts were extracted and perfused in a nonrecycling manner for 10 min with 35 mM NaCI, 4.75 mM KCl, 1.2 mM KH2PO4, 150 mM sucrose, 25 mM NaHCO3, 10 mM HEPES buffer, 10 mM glucose, and 5 g/liter albumin bovine fraction V (pH 7.4, 370 C, 95% 02/5% CO2).9 A recycling perfusion (25 min) was carried out with the same solution also containing 150 U/ml unpurified collagenase (E.C.3.4.4.19.) and 1000 U/ml hyaluronidase (E.C.3.2.1.36.).At the end of the perfusion the softened heart was sliced into small pieces and reincubated for 10 min in the same enzymecontaining solution; the suspension was filtered through a nylon mesh and centrifuged gently for 2 min at 50 g. The supernatant was removed and the pellet was washed three times in 130 mM NaCl, 4.0 mM KCI, 1.2 mM KH2PO4, 25 mM HEPES buffer, 10 mM glucose, and 20 g/liter albumin bovine fraction V (pH 7.4, room temperature, 100% 02). A small population of completely destr...
1-11C-n-Butanol produced semiautomatically using a cyclotron was employed to investigate the whole-body distribution and kinetics of the label of this compound. Following the administration of 11C-butanol into the aorta of two dogs, more than 80% of the activity was cleared from the blood within 1 min. The activity distribution mirrored the cardiac output distribution as determined using 121I microspheres. Within 25 min p.i., a significant release of decay-corrected activity was only observed for the liver, spleen, and kidneys. Muscle and whole-body activity showed constant levels during this period. In 45 tumor transplants from rats, the dynamic behavior of the label was studied. The tissue retention of activity following injection into the a. femoralis was approximately 100% during the 1st 15 s for both tumor and muscle (n = 6). The activity release by tumors during the 1st 10 min after intra-aortic injection was 18% +/- 4.5% (n = 39; decay corrected). In five different tumor lines (n = 10), the initial 11C-butanol uptake was related to that of muscle, and the results were correlated with the tumor-to-muscle retention of 121I-microspheres (r = 0.89). In 17 tumors, the correlation between 11C-butanol uptake and the washout rate of 133Xe resulted in a correlation coefficient of 0.96. Tumor-to-muscle uptake ratios could be equally determined using intra-aortic and intravenous injection, as evaluated by intraindividual comparison in 12 rats (y = 0.01 + 0.98x; r = 0.98). 11C-Butanol appears to be an appropriate radiotracer for the assessment of blood supply to malignant tumors relative to muscle.
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