Metabolic fate of radioiodinated heptadecanoic acid in the normal canine heart.

Abstract

To clarify the metabolic fate of radioiodinated heptadecanoic acid in myocardium, the time course and distribution of the radioactivity over '311-heptadecanoic acid, free radioiodide, and various lipids (with incorporated iodoheptadecanoic acid) were determined in normal canine myocardium. In 10 dogs seven biopsy specimens were taken over 30 min after injection of 1311-heptadecanoic acid. The radioactivity in the specimens increased until the fifth minute and decreased thereafter, with a half-time of 36 min. In the fifth minute, 61% of the radioactiviy was free iodide, and its curve paralleled the curve of the total radioactivity. As early as the first minute 13'I-heptadecanoic acid activity was reduced to 14% and decreased further. Activity of radioiodinated phospholipids, (mono, di, tri)-glycerides, and cholesterol-esters remained constant after an initial increase. These results indicate that immediately after uptake, '3'I-heptadecanoic acid is either metabolized, liberating the radioiodide, or stored in lipids. Because the activity of radiolabeled lipids remained constant during the study period and because iodide activity paralleled the total activity in biopsy specimens, it is concluded that in normal myocardium, washout of free radioiodide determines the elimination rate as observed during a scintigraphic study. Thus the elimination rate cannot be related to the ,8-oxidation rate as previously supposed. Circulation 72, No. 3, 565-71, 1985. THE HEART uses a variety of substances like glucose, free fatty acids, and lactate as an energy source for its metabolism. Under normal physiologic conditions, 60% to 80% of energy-rich phosphate bonds are derived from oxidation of long-chain free fatty acids.' Therefore long-chain free fatty acids labeled with a radioisotope were proposed as indicators of cardiac metabolism in vivo. One of these radiolabeled free fatty acids was heptadecanoic acid (HDA) labeled with 123I in the omega position.It was found that after administration of radiolabeled HDA, regional elimination of the radioactivity differed under various pathophysiologic conditions of the myocardium. In ischemic myocardium the elimination rate was found to be lower than that in comparable normal myocardium.A-"0 In some patients with a recently sustained infarction, a higher elimination rate Two hypotheses have been developed to explain the observed differences in elimination rates. Both hypotheses are related to cardiac metabolism of radioiodinated free fatty acids. After uptake in the myocyte, radioiodinated long-chain free fatty acids are degraded by /3-oxidation'4 in the mitochondria. Radioiodine is split off and leaves the cell.In the first hypothesis the elimination rate is related to the /-oxidation rate of the radioiodinated fatty acids'5 in the mitochondria. In the second hypothesis the elimination rate is related to the diffusion rate of radioiodide from the myocardial mitochondria into the systemic circulation. 6 Because knowledge of the underlying mechanism is important for interpretat...

The Fate of 131I-17-lodohepta-decanoic Acid During Lactate Loading: Its Oxidation is Strongly Inhibited in Favor of its Esterification

“…In that case, the turnover rate of the triglycerides should be faster than that of the fatty acids. Support for this opinion were findings in an earlier study: in control dogs, myocardial biopsies taken within the first 5 min showed that the percentage of labelled triglycerides was lower than the oxidized part (21). The present study demonstrates that at raised lactate levels the fatty acid triglyceride fatty acid cycle is strongly involved in contrast to the fasted state.…”

“…In the present and earlier studies (21) it was found that under fasted conditions m I-17-HDA was oxidized to the same extent (60-70%) as the natural fatty acids (7). It was demonstrated that the time course of total myocardial radioactivity was not related to the beta-oxidation rate of 1 3 1 I-17-HDA, but to the diffusion of the uncoupled isotope from the cardiac cell into the circulation (21). It meant that the fate of the label did not mirror the metabolic fate of the traced substance (16,21).…”

“…It was demonstrated that the time course of total myocardial radioactivity was not related to the beta-oxidation rate of 1 3 1 I-17-HDA, but to the diffusion of the uncoupled isotope from the cardiac cell into the circulation (21). It meant that the fate of the label did not mirror the metabolic fate of the traced substance (16,21). However, a relation could be established between the externally measured time-activity curve and the biochemical fate of the labelled fatty acid (6).…”

Metabolic imaging using SPECT

“…However, their ability to assess myocardial metabolism has been questioned. A canine study revealed that myocardial counts peaked at 5 min after 131 I-IHDA infusion to the left atrium followed by decrease with a half life of 36 min, although, the myocardial activity of radiolabeled fatty acids remained constant after an initial increase, indicating that washout rate of radioactivity from the heart is determined by the back diffusion of deiodinated free iodine not by ß-oxidation [17]. A clinical study using IHDA demonstrated high quality image early after injection, but the image quality deteriorated rapidly because of rapid reduction of myocardial counts and increase in background counts by deiodinated radioiodine [18].…”

Tracers for metabolic imaging of brain and heart

“…1987;Wyns etal. Elimination of the free halide coming either from direct//-oxidation (first fast elimination phase) or from //-oxidation after return from the lipid pool (second slow elimination phase) is the rate-determining step for these co-halogenated aliphatic fatty acids (Kloster and St6cklin 1982;Kloster et al 1984;Visser et al 1985). Substrate utilization and hence the kinetics of elimination are also strongly dependent on the nutritional supply of the heart muscle and on metabolic and pathologic changes (Schelbert et al 1983).…”