Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono beta) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono beta into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.     

Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.     

Do iodinated fatty acids undergo a nonspecific deiodination in the myocardium?

The intracellular and subcellular distribution of 16-(123I)-iodo-9-hexadecenoic acid were studied in isolated rat hearts, perfused with or without glucose. At various time intervals after injection, cardiac lipids were extracted and the activity was determined for all fractions and all lipid classes. The total cardiac activity was maximal within 1 min postinjection and most of the activity was in the aqueous phase. The presence of glucose in the perfusion medium induced an increase of total cardiac and organic fraction activities. In the latter fraction, activity was very low for FFA, but high for triglycerides (TG), and especially polar lipids. The presence of an exogenous substrate, led to a more active esterification of fatty acids. Coronary effluent analysis showed, in the hydrophilic phase, a lower activity spike in the presence than in the absence of glucose. In the mitochondrial fraction most activity occurred in the organic phase, especially as polar lipids. In the nonmitochondrial fraction, activity was much higher in the aqueous phase. At 90 s postinjection of 1-14C-palmitic acid, over 80% of the myocardial activity was found in the hydrophilic fraction, which indicates, as for the iodo-fatty acid (IFA), an immediate and important oxidation, especially without glucose. These data seem to prove that IFA is taken up by the myocardial cell, subsequently enters the mitochondria and, without an early deiodination, is oxidized with iodide release. Changes in IFA metabolism, consecutive to modifications of glucose concentration in the perfusion medium can be observed by external detection of the myocardial activity curve. Omega-Iodinated fatty acids do not undergo a nonspecific deiodination and are therefore well suited for an external study of myocardial metabolism.     

Effect of glucose on the distribution of iodine-123-IHA-16 between esterification and oxidation in canine myocardium

To evaluate the effect of glucose perfusion on the myocardial metabolism of [123I]-16-iodo-9-hexadecenoic acid (IHA), the latter was injected intravenously into six fasting dogs perfused with a solution lacking glucose (controls) and seven fasting dogs perfused with glucose and insulin. The distribution of myocardial 123I among iodides, free IHA, and esterified IHA was measured in myocardial biopsy specimens. The increase in esterification and decrease in oxidation of IHA due to glucose were quantified using a compartmental mathematical model of myocardial IHA metabolism. Subsequently, in six control and six glucose-perfused dogs, cardiac radioactivity was measured with a scintillation camera for 1 hr following i.v. injection of IHA. Four different methods were used to analyze the myocardial time-activity curves and to calculate the distribution of IHA between oxidation and esterification. Results comparable to those provided by analysis of biopsy specimens can be obtained by considering the curve to be the sum of an exponential and a constant, or by analyzing it with a compartmental mathematical model.     

The kinetics of beta-methyl-substituted labelled fatty acids in ischaemic myocardium: an analysis in man and with a blood-perfused isolated heart model.

beta-Methyl-substituted free fatty acids (FFAs) have been developed for myocardial single-photon emission tomography (SPET) imaging, but little is known about their kinetics in ischaemic conditions. The aim of this study was to determine the changes in the myocardial kinetics of a beta-methyl-branched FFA, [123I]16-iodo-3-methyl-hexadecanoic acid (MIHA), under ischaemic conditions. The kinetics of MIHA were analysed: (a) using a blood-perfused isolated heart model subjected to moderate ischaemia (50% flow reduction) and (b) in patients who had an exercise thallium-201 SPET defect corresponding to either necrotic (n = 13) or chronically ischaemic and viable (n = 15) myocardium, and who underwent two consecutive SPET studies after MIHA injection. In animals, the myocardial early retention fraction of MIHA, but not its clearance rate, was dependent on coronary flow, the early retention fraction being higher in ischaemic than in normoxic conditions (0.24 +/- 0.10 vs 0.14 +/- 0.04, P = 0.004). In the patient SPET studies, the uptake of MIHA calculated in ischaemic and viable areas (G1: 74% +/- 9% of maximal left ventricular value) was different from that calculated in necrotic (G2: 59% +/- 7%, P < 0.001) or normal (G3: 88 +/- 6%, P < 0.001) areas. By contrast, MIHA-clearance calculated between the two consecutive SPET studies was not different in G1, G2 and G3. Unlike in the case of other FFAs, the myocardial clearance of MIHA is not decreased by ischaemia. However, the early retention of MIHA is increased in the case of a moderate reduction in coronary flow, a property which might help in the detection of viability in chronically ischaemic myocardium.     

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be beta oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be beta oxidized only after an initial alpha oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me2) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me2) which cannot be beta oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-14C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid greater than 16-iodo-3-R,S-methyl palmitic acid greater than 16-iodo-2-R,S-methyl palmitic acid greater than 16-iodo-2,2-dimethyl palmitic acid greater than 16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethyl-branched iodo fatty acids as compared to the monomethyl ones and palmitic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kinetics of iodomethylated hexadecanoic acid metabolism in the rat myocardium: influence of the number and the position of methyl radicals

The methyl-branched fatty acids, if radioiodine labelled in alpha position, are potentially adapted to a selective study of FA myocardial uptake. To determine the position and the number of methyl radicals that are necessary to obtain a maximal uptake and a minimal degradation, we measured time-activity evolution of isolated and perfused rat hearts after an injection of iodinated fatty acids which are mono- or dimethylated in alpha or beta position. Except for dimethyl fatty acid, the uptake is similar for all fatty acids studied to that of the straight chain analogue; beta mono- or dimethyl fatty acids seem best adapted to a study of the uptake because alpha monomethyl fatty acids undergo a metabolic degradation and alpha mono- and dimethyl fatty acids induce ventricular fibrillations.     

Evaluation of fatty acid metabolism in hearts after ischemia-reperfusion injury using a dual-isotope autoradiographic approach and tissue assay for metabolites of tracer.

We investigated whether changes in myocardial uptake of fatty acid tracer after reperfusion following transient myocardial ischemia were closely related to alterations in intracellular fatty acid oxidation. METHODS: Using a fatty acid tracer of (131)I- and (125)I-labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA), the myocardial uptake and metabolites were determined by dual-tracer autoradiography and thin-layer chromatography in rats 3 or 14 d after reperfusion following 5 or 15 min of ischemia induced by coronary artery ligation. RESULTS: 9MPA metabolites processed via beta-oxidation were lower in the ischemic region (IR) than in non-IR 3 d after 5 min of ischemia, despite no reduction of tracer uptake in IR. Oxidation of 9MPA was recovered 14 d after 15 min of ischemia in association with normalization of tracer uptake in IR, whereas both uptake and oxidation of 9MPA were markedly impaired 3 d after 15 min of ischemia, accompanied by slow clearance of myocardial tracer. CONCLUSION: Normal uptake of fatty acid tracer early after reperfusion does not always imply preserved intracellular fatty acid oxidation. However, reduction of tracer uptake might reflect impaired fatty acid oxidation.     

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be oxidized only after an initial oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me₂) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me₂) which cannot be oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-¹⁴C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid >16-iodo-3-R,S-methyl palmitic acid>16-iodo-2-R,S-methyl palmitic acid>16-iodo-2,2-dimethyl palmitic acid>16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethylbranched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[¹²⁵I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1-¹⁴C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched-palmitic acids were found in hepatocyte or secred phospholipids as compared with palmitic acid. This metabolic fate of methyl-branched iodo palmitic acids argues against their utilization as imaging probes to monitor in vivo the synthesis and the secretion of triglycerides by the liver.     

The kinetics of β-methyl-substituted labelled fatty acids in ischaemic myocardium: an analysis in man and with a blood-perfused isolated heart model

β-Methyl-substituted free fatty acids (FFAs) have been developed for myocardial single-photon emission tomography (SPET) imaging, but little is known about their kinetics in ischaemic conditions. The aim of this study was to determine the changes in the myocardial kinetics of a β-methyl-branched FFA, [¹²³I]16-iodo-3-methyl-hexadecanoic acid (MIHA), under ischaemic conditions. The kinetics of MIHA were analysed: (a) using a blood-perfused isolated heart model subjected to moderate ischaemia (50% flow reduction) and (b) in patients who had an exercise thallium-201 SPET defect corresponding to either necrotic (n = 13) or chronically ischaemic and viable (n = 15) myocardium, and who underwent two consecutive SPET studies after MIHA injection. In animals, the myocardial early retention fraction of MIHA, but not its clearance rate, was dependent on coronary flow, the early retention fraction being higher in ischaemic than in normoxic conditions (0.24±0.10 vs 0.14±0.04, P = 0.004). In the patient SPET studies, the uptake of MIHA calculated in ischaemic and viable areas (G1: 74%±9% of maximal left ventricular value) was different from that calculated in necrotic (G2: 59%±7%, P<0.001) or normal (G3: 88±6%, P<0.001) areas. By contrast, MIHA-clearance calculated between the two consecutive SPET studies was not different in G1, G2 and G3. Unlike in the case of other FFAs, the myocardial clearance of MIHA is not decreased by ischaemia. However, the early retention of MIHA is increased in the case of a moderate reduction in coronary flow, a property which might help in the detection of viability in chronically ischaemic myocardium. Received 3 November 1998 and in revised form 15 January 1999     

Metabolic myocardial viability assessment with iodine 123-16-iodo-3-methylhexadecanoic acid in recent myocardial infarction: Comparison with thallium-201 and fluorine-18 fluorodeoxyglucose

The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methyl-hexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and to evaluate its contribution compared with the²⁰¹Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection²⁰¹T1 imaging, rest MIHA imaging and glucoseloaded FDG imaging were performed in 22 patients with recent myocardial infarction. Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum uptake on stress²⁰¹T1 imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a)²⁰¹T1 activity during exercise, redistribution and reinjection and (b) MIHA up-take, using the two FDG thresholds most commonly considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that²⁰¹T1 reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85 and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively;P<0.05 vs other tests). The global predictive values of MIHA and²⁰¹T1 reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments were considered,²⁰¹T1 reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold,P<0.05 vs²⁰¹T1 reinjection). In all circumstances, MIHA was less specific than²⁰¹T1 reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA accurately detects the persistence of metabolic viability, but is not superior to²⁰¹T1.     

Mathematical model of the metabolism of 123I-16-iodo-9-hexadecenoic acid in an isolated rat heart. Validation by comparison with experimental measurements

The aim of the present study was to demonstrate that it is possible to estimate the intracellular metabolism of a fatty acid labelled with iodine using external radioactivity measurements. ¹²³I-16-iodo-9-hexadecenoic acid (IHA) was injected close to the coronary arteries of isolated rat hearts perfused according to the Langendorff technique. The time course of the cardiac radioactivity was measured using an INa crystal coupled to an analyser. The obtained curves were analysed using a four-compartment mathematical model, with the compartments corresponding to the vascular-IHA (O), intramyocardial free-IHA (1), esterified-IHA (2) and iodide (3) pools. Curve analysis using this model demonstrated that, as compared to substrate-free perfusion, the presence of glucose (11 mM) increased IHA storage and decreased its oxidation. These changes were enhanced by the presence of insulin. A comparison of these results with measurements of the radioactivity levels within the various cellular fractions validated our proposed mathematical model. Thus, using only a mathematical analysis of a cardiac time-activity curve, it is possible to obtain quantitative information about IHA distribution in the different intracellular metabolic pathways. This technique is potentially useful for the study of metabolic effects of ischaemia or anoxia, as well as for the study of the influence of various substrates or drugs on IHA metabolism in isolated rat hearts.     

Effect of 3-methyl-branching on the metabolism in rat hearts of radioiodinated iodovinyl long chain fatty acids

The metabolism of two new 3-methyl-branched iodovinyl fatty acids in rat hearts was evaluated by determining the subcellular and lipid pool distribution of these radiolabeled analogues after intravenous injection. Methyl branching had been introduced into the straight chain analogue, 19-iodo-18-nonadecenoic acid (IVN), to produce the monomethyl analogue, 19-iodo-3-(R,S)-methyl-18-nonadecenoic acid (BMIVN) and the dimethyl derivative, 19-iodo-3,3-dimethyl-18-nonadecenoic acid (DMIVN) in the hope of inhibiting beta oxidation. Since the presence of 3-methyl branching results in delayed myocardial clearance in rats, differences were sought in the lipid and subcellular distribution of these branched analogues that might correlate with the prolonged retention and reflect differences in metabolism. Hearts of rats injected intravenously with the radiolabeled fatty acids were removed and homogenized and the homogenates partitioned between the chloroform-methanol (organic) fraction and the aqueous fraction. Comparison of the distribution of radioactivity between the organic and aqueous fractions showed that most of the DMIVN and BMIVN activity was in the organic fraction with IVN activity initially divided equally between the two fractions. Identification of the lipid components of these organic fractions showed that there was slow incorporation of DMIVN into the triglyceride and polar lipid fractions with a slow loss from the free fatty acid fraction. With the straight chain IVN analogue which shows rapid washout from rat hearts, there was loss of activity from all 3 lipid components during the 60 min. The monomethyl branched BMIVN analogue demonstrated predominant storage in the polar lipid fraction with some incorporation into triglycerides.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sequential sampling: a new acquisition technique for fatty acid kinetics from quasi-simultaneous multiple projections

Studies of myocardial metabolism by rapidly catabolized fatty acids like omega-I-123-heptadecanoic acid (IHA) are usually limited to one planar view of require sophisticated equipment, such as bidirectional slant-hole collimators or seven-pinhole collimators for multiplane or tomographic views. To solve this problem a normal SPECT camera was utilized to acquire sequentially sampled dynamic studies from up to six different views. This was done by a periodically repeated sequence of acquisitions in different projections, which followed one another clockwise. This procedure overcomes the single-plane limitations of the usual IHA dynamic studies. It reveals regional myocardial patterns of tracer uptake and elimination not obtainable from any single viewing angle. In this way one methodological disadvantage relative to thallium perfusion studies is removed. Furthermore, the non-invasive diagnosis of cardiomyopathies, for which no other radioisotope procedure is appropriate, should be improved using this new method.     

I-123 heptadecanoic acid — value and limitations in comparison with C-11 palmitate

To define the potential of ¹²³I-labeled heptadecanoic acid (IHA) for the noninvasive assessment of myocardial free fatty acid (FFA) metabolism, the kinetics of IHA were compared to those of physiologic ¹¹C-palmitate (CPA). The single-pass myocardial extraction fraction of IHA was lower than that of CPA (0.53±0.11 vs 0.65±0.10 under control conditions). Following an intracoronary injection of IHA and CPA, the myocardial time-activity curves showed biphasic clearance of both tracers. While, for CPA, the half-time of the early phase of the time-activity curve was a function of myocardial oxygen consumption (MVO₂), this phase was not found to reflect the oxidative metabolism of IHA. However, for both tracers, the size of the early phase increased with augmented MVO₂, whereas the size of the late phase decreased. The late phase represents storage of both tracers in triglycerides and phospholipids. Hence, while quantitative measurement of CPA oxidation is possible from the early phase of the time-activity curve, only the ratio between the size of the early and late phase might be of value in assessing myocardial FFA metabolism using IHA.

     

I-123 labeled hexadecenoic acid in comparison with Thallium-201 for myocardial imaging in coronary heart disease

The imaging properties of ¹²³I-16-iodo-9-hexadecenoic acid (¹²³I-HA), a terminally iodinated 17-carbon atom fatty acid analogue, were compared with Thallium-201 (²⁰¹Tl). Because of its shorter half-life, favourable photon-energy and rapid myocardial turnover rate, ¹²³I-HA possesses potential advantages in the study of regional myocardial perfusion and metabolism. Twelve patients with documented coronary artery disease (CAD) were studied; eight patients sustained an acute myocardial infarction, four patients suffered from unstable angina. Visually assessed, a similar distribution pattern and comparable imaging quality was demonstrated with both radionuclides. The scintigraphic results were also correlated with coronary arteriographic findings. A good relationship was found between the perfusion defects and the location of the coronary artery lesions in the patients with acute myocardial infarction.We conclude that ¹²³I-HA is comparable to ²⁰¹Tl in detecting areas of reduced myocardial perfusion in patients with CAD with the advantage of studying myocardial metabolism.     

Synthesis and preliminary evaluation of (18)F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation

Interest remains strong for the development of a noninvasive technique for assessment of regional fatty acid oxidation rate in the myocardium. (18)F-labeled 4-thia palmitate (FTP, 16-[(18)F]fluoro-4-thia-hexadecanoic acid) has been synthesized and preliminarily evaluated as a metabolically trapped probe of myocardial fatty acid oxidation for positron emission tomography (PET). The radiotracer is synthesized by Kryptofix 2.2.2/K(2)CO(3) assisted nucleophilic radiofluorination of an iodo-ester precursor, followed by alkaline hydrolysis and by purification by reverse phase high performance liquid chromatography. Biodistribution studies in rats showed high uptake and long retention of FTP in heart, liver, and kidneys consistent with relatively high fatty acid oxidation rates in these tissues. Inhibition of carnitine palmitoyl-transferase-I caused an 80% reduction in myocardial uptake, suggesting the dependence of trapping on the transport of tracer into the mitochondrion. Experiments with perfused rat hearts showed that the estimates of the fractional metabolic trapping rate (FR) of FTP tracked inhibition of oxidation rate of palmitate with hypoxia, whereas the FR of the 6-thia analog 17-[(18)F]fluoro-6-thia-heptadecanoic acid was insensitive to hypoxia. In vivo defluorination of FTP in the rat was evidenced by bone uptake of radioactivity. A PET imaging study with FTP in normal swine showed excellent myocardial images, prolonged myocardial retention, and no bone uptake of radioactivity up to 3 h, the last finding suggesting a species dependence for defluorination of the omega-labeled fatty acid. The results support further investigation of FTP as a potential PET tracer for assessing regional fatty acid oxidation rate in the human myocardium.     

Sequential sampling: A new acquisition technique for fatty acid kinetics from quasi-simultaneous multiple projections

Studies of myocardial metabolism by rapidly catabolized fatty acids like -I-123-heptadecanoic acid (IHA) are usually limited to one planar view of require sophisticated equipment, such as bidirectional slant-hole collimators or seven-pinhole collimators for multiplane or tomographic views. To solve this problem a normal SPECT camera was utilized to acquire sequentially sampled dynamic studies from up to six different views. This was done by a periodically repeated sequence of acquisitions in different projections, which followed one another clockwise. This procedure overcomes the single-plane limitations of the usual IHA dynamic studies. It reveals regional myocardial patterns of tracer uptake and elimination not obtainable from any single viewing angle. In this way one methodological disadvantage relative to thallium perfusion studies is removed. Furthermore, the non-invasive diagnosis of cardiomyopathies, for which no other radioisotope procedure is appropriate, should be improved using this new method.     

Effect of 3-methyl-branching on the metabolism in rat hearts of radioiodinated iodovinyl long chain fatty acids

The metabolism of two new 3-methyl-branched iodovinyl fatty acids in rat hearts was evaluated by determining the subcellular and lipid pool distribution of these radiolabeled analogues after intravenous injection. Methyl branching had been introduced into the straight chain analogue, 19-iodo-18-nonadecenoic acid (IVN), to produce the monomethyl analogue, 19-iodo-3-(R,S)-methyl-18-nonadecenoic acid (BMIVN) and the dimethyl derivative, 19-iodo-3,3-dimethyl-18-nonadecenoic acid (DMIVN) in the hope of inhibiting oxidation. Since the presence of 3-methyl branching results in delayed myocardial clearance in rats, differences were sought in the lipid and subcellular distribution of these branched analogues that might correlate with the prolonged retention and reflect differences in metabolism. Hearts of rats injected intravenously with the radiolabeled fatty acids were removed and homogenized and the homogenates partitioned between the chloroform-methanol (organic) fraction and the aqueous fraction. Comparison of the distribution of radioactivity between the organic and aqueous fractions showed that most of the DMIVN and BMIVN activity was in the organic fraction with IVN activity initially divided equally between the two fractions. Identification of the lipid components of these organic fractions showed that there was slow incorporation of DMIVN into the triglyceride and polar lipid fractions with a slow loss from the free fatty acid fraction. With the straight chain IVN analogue which shows rapid washout from rat hearts, there was loss of activity from all 3 lipid components during the 60 min. The monomethyl branched BMIVN analogue demonstrated predominant storage in the polar lipid fraction with some incorporation into triglycerides. Subcellular distribution studies of the three analogues also showed differences that correlated with the observed differences in heart retention properties. With the unbranched IVN analogue, radioactivity was found primarily in the cytoplasmic fraction 30 min after injection, whereas the branched analogues demonstrated a much higher association with the microsomal and mitochondrial fractions of the heart. In rats fed prior to injection, these differences in the subcellular distribution profiles were minimized. The lipid and subcellular distribution patterns reported here for the methyl branched analogues as compared to those of the straight chain iodovinyl fatty acid may provide some understanding as to the mechanisms of retention in rat myocardium.Research supported by the Office of Health and Environmental Research, U.S. Department of Energy, under contract DE-AC0 5-840 R21400 with Martin Marietta Energy Systems, Inc.     

A comparison between terminally radioiodinated hexadecenoic acid (125I-HA) and heptadecanoic acid (131I-H0A) in the dog heart

The regional myocardial distribution of ¹²⁵I-16-iodo-9-hexadecenoic acid (¹²⁵I-HA) and ¹³¹I-17-iodo-heptadecanoic acid (¹³¹I-H⁰A) was determined in one normal dog and in five dogs within 5 min after coronary artery occlusion. The total myocardial uptake of ¹²⁵I-H A was about 40% lower than that of ¹³¹I-H⁰A. The ratio ¹²⁵I:¹³¹I in the normally perfused parts of the myocardium was 0.38–0.81, but the ischemic tissue showed a higher ¹²⁵I:¹³¹I-¹³¹I ratio (0.87–1.03), due to lower accumulation of ¹³¹I-H⁰A in ischemic myocardium. We conclude that both radioiodinated fatty acids are reliable indicators of myocardial perfusion and that iodo-heptadecanoic acid, when labeled with ¹²³I, may be preferred to iodo-hexadecenoic acid as the labeled fatty acid for cardiac imaging agent in clinical practice.