Comparison of the transport of 42K+, 22Na+, 201Tl+, and [99mTc(dmpe)2 X Cl2]+ using human erythrocytes.

The ability of isolated human erythrocytes to exchange Na+ for K+ via (Na+ + K+)-ATPase was used to study the characteristics and interactions of the transport of both alkali metal and synthetic monovalent cations. Both efflux and influx studies were carried out and the results showed that: (1) Efflux of 22Na+ from human erythrocytes was stimulated by the addition of either of K+, or Tl+ at 10 mM and inhibited by the addition of ouabain. Unlabeled K+ and the addition of [99Tc(dmpe)2 X Cl2]+ (dmpe, 1,2-bis(dimethylphosphino)ethane) at 5 mM had no effect on 22Na+ efflux. (2) Influx of 42K+ was inhibited by the addition of ouabain, unlabeled K+, or Tl+. 201Tl+ influx was more rapid and of a greater magnitude than 42K+ influx. [99Tc(dmpe)2 X Cl2]+ had no effect on 42K+ uptake. (3) Influx of 201Tl+ was inhibited by ouabain and by the addition of unlabeled Tl+. Addition of [99Tc(dmpe)2 X Cl2]+ at 5 mM resulted in an inhibition of 201Tl+ influx. (4) [99Tc(dmpe)2 X Cl2]+ influx resembled that of 42K+ with respect to rate and magnitude. Influx of [99mTc(dmpe)2 X Cl2]+ was shown to be unaffected by ouabain, unlabeled K+ or Tl+. Addition of 5 mM [99Tc(dmpe)2 X Cl2]+ initially had no effect on [99mTc(dmpe)2 X Cl2]+ influx, however, a time-dependent stimulation of the influx of the [99mTc(dmpe)2 X Cl2]+ was observed. We conclude that the influx of the various alkali, metal and synthetic monovalent cations into erythrocytes is mediated by different mechanisms. Most clearly, the influx of [99mTc(dmpe)2 X Cl2]+ is not by a mechanism similar to that of utilized by K+ or Tl+.

Rat model for acute myocardial infarction: application to technetium-labeled glucoheptonate, tetracycline, and polyphosphate.

Cauterization of rat myocardium serves as a quick (2 min) inexpensive technique to create an animal model of acute myocardial infarction useful in evaluating radiopharmaceuticals as potential clinical imaging agents. Preliminary evidence indicates that is correlates well with behavior in man. Application of the model led to the discovery, confirmed by later investigators, that chelating agents such as glucoheptonate and polyphosphate show significant uptake in recent myocardial lesions.

Myocardial imaging with technetium-99m CPI: initial experience in the human.

The hexakis(isonitrile)technetium(I) analog [99mTc]carbomethoxyisopropyl isonitrile (CPI) has high myocardial uptake and rapid lung and liver clearance in most animal species. To evaluate [99mTc]CPI as a myocardial imaging agent in the human, we evaluated this tracer in three normals and in six patients with coronary artery disease (CAD). In normals, [99mTc]CPI cleared quickly from the lungs and accumulated in the liver and heart. The liver activity peaked at 10-15 min and cleared through the hepatobiliary system. Planar images were of excellent technical quality with high myocardial to background ratios as early as 10 min after injection. Myocardial activity fell gradually to 76.1 +/- 2.9 (s.d.)% of initial activity by 60 min after injection. In six patients with CAD, myocardial defects were present on planar images up to 2 hr after exercise and injection. In one out of six patients, the defect was not seen 3 hr after injection. In five of the six patients, normal perfusion patterns were observed 1 hr after reinjection of CPI at rest (4 hr after the initial injection). In one patient who developed spontaneous angina prior to reinjection, the perfusion defects persisted. The repeat study 3 days later with injection of [99mTc]CPI at rest was normal. Technetium-99m CPI appears to have excellent physical and biologic properties for use in association with myocardial imaging with exercise.

Simultaneous measurement of ventricular function and myocardial perfusion using the technetium-99m isonitriles.

To assess both ventricular function and myocardial perfusion, five normal volunteers, 19 patients with coronary artery disease, and two patients with cardiomyopathy and normal coronary arteries were injected with 20 mCi of Tc-99m isonitrile (either methoxyisobutyl isonitrile or carbomethoxyisopropyl isonitrile) at peak bicycle exercise and again at rest. A standard Tl-201 stress test was performed in all patients at the same level of exercise within one month of the isonitrile study. In all normal subjects, myocardial perfusion was normal at stress levels and the left ventricular ejection fraction increased 5% or more with exercise. In the 19 patients with coronary artery disease, the ejection fraction response to exercise was abnormal in 14 patients. Perfusion images with the Tc-99m isonitriles correlated well with Tl-201 images during exercise and at rest, with 89% concordance in areas of ischemia or infarction and 93% in normal segments. A simultaneous study of myocardial perfusion and ventricular function can be performed using a single Tc-99m labeled myocardial agent. Tc-99m isonitriles, particularly Tc-99m MIBI, result in sufficiently high photon flux that ventricular performance can be studied at peak exercise and again during rest using the first pass method.

Myocardial perfusion imaging with a new radiotracer, technetium-99m-hexamibi (methoxy isobutyl isonitrile): comparison with thallium-201 imaging.

Technetium-99m-hexamibi (methoxy isobutyl isonitrile) is a Tc-99m-hexakis analog that can be used as a myocardial perfusion imaging agent. This is a report of an initial study that was performed in four institutions to assess the feasibility of Tc-99m-hexamibi myocardial imaging for the detection of coronary artery disease in patients undergoing treadmill stress test. Thirty-three patients referred for evaluation of chest pain had two exercise stress tests, one with Tl-201 and at least 24 hours after, and a second one with Tc-99m-hexamibi. Myocardial planar imaging started 60 minutes after injection at stress of 10-20 mCi of Tc-99m-hexamibi. Because this agent does not redistribute in myocardium after a stress injection, a second injection of 10-20 mCi of Tc-99m-hexamibi was performed with the patient at rest a few days later. Qualitative assessment of both Tl-201 and Tc-99m-hexamibi myocardial distribution was performed in 297 left ventricle segments (three segments of each of three views). There was a good correlation for the presence of normality, scar, or ischemia with the two radiopharmaceuticals, both on a segment by segment (259/297, or 87.2%) and patient-by-patient basis (29/33, or 87.9%). The number of segments found ischemic with Tl-201 and with Tc-99m-hexamibi were nearly equal, as were the number that were normal with one radiopharmaceutical and ischemic by the other. This initial study demonstrates that it is possible to detect stress-induced abnormalities of myocardial perfusion with Tc-99m-hexamibi similar to Tl-201 imaging.