Myocardial viability--what is the definition?
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Biomedical subjects
Publications and source records attributed to R J Gropler.
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The rate of clearance of myocardial carbon-11 (11C) activity (after the administration of 11C-acetate) has been shown to correlate closely with myocardial oxygen consumption. In the present study, we hypothesized that regional net myocardial uptake of 11C-acetate, which reflects primarily delivery and extraction of tracer, would be markedly flow-dependent and potentially useful as an indirect index of regional myocardial blood flow. In 22 patients with stable coronary artery disease, the regional distribution of early net uptake of 11C-acetate was correlated with estimates of regional myocardial blood flow assessed with oxygen-15-water. The myocardial images of 11C-acetate uptake were of high quality. The correlation between the two approaches was close (r = 0.88) and not affected by the metabolic state of the tissue. Thus, in patients with stable coronary artery disease, under resting conditions, direct estimates of myocardial oxygen consumption in relation to the level of delivery of tracer to the tissue can now be obtained by PET with use of a single radiopharmaceutical, 11C-acetate. This approach may prove particularly useful in streamlining clinical protocols designed to assess myocardial oxygen consumption.
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.
In initial studies using fluorine-18-fluorodeoxyglucose (FDG) in normal fasted subjects, we observed disparities in the regional myocardial accumulation of this tracer. Accordingly, we systematically evaluated regional myocardial FDG accumulation in comparison with regional myocardial perfusion assessed with oxygen-15-water and oxidative metabolism assessed with carbon-11-acetate in nine normal subjects (four studied after a 5-hr fast and five studied both fasted and following glucose loading). Under fasting conditions, myocardial accumulation of FDG in the septum and anterior wall averaged 80% of that in the lateral and posterior walls (p less than 0.03). In contrast, after glucose loading the regional distribution of myocardial FDG accumulation became more homogeneous. Regional myocardial perfusion, oxidative metabolism, and accumulation of carbon-11-acetate were homogeneous under both conditions. Thus, under fasting conditions there are regional variations in myocardial accumulation of FDG, which are visually apparent, are not associated with concomitant changes in oxidative metabolism or perfusion, and cannot be attributed to partial-volume effects. This significant heterogeneity may limit the specificity of PET with FDG for detecting myocardial ischemia in fasting subjects.
Positron emission tomography (PET) with fluorine 18-labeled fluorodeoxyglucose (FDG) has provided important insights into the alterations in myocardial glucose metabolism associated with normal cardiac physiology and pathophysiology. In patients with left ventricular dysfunction caused by coronary artery disease, PET-FDG studies have identified certain patterns of myocardial glucose metabolism relative to flow that are associated with viable myocardium. Consequently, in many centers, PET-FDG imaging is being used to identify patients with left ventricular dysfunction who are likely to benefit from coronary revascularization. However, myocardial glucose metabolism (and thus myocardial uptake of FDG) is markedly dependent on a variety of factors, particularly the substrate environment and level of myocardial perfusion. These and other factors must be considered to obtain and interpret myocardial FDG images accurately with respect to the underlying pathophysiologic process. In this review the impact of these factors on myocardial FDG imaging, as well as the relative advantages and disadvantages of approaches designed to optimize myocardial PET-FDG studies, will be discussed.