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1.
Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes   总被引:1,自引:0,他引:1  
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)  相似文献   

2.
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.  相似文献   

3.
Iodomethylated fatty acid metabolism in mice and dogs   总被引:2,自引:0,他引:2  
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.  相似文献   

4.
Myocardial metabolism of radioiodinated methyl-branched fatty acids   总被引:3,自引:0,他引:3  
Methylated fatty acids labeled with radioactive iodine have been proposed as a means of studying regional myocardial uptake of fatty acids in man. To investigate the methylated fatty acid that is best adapted for an assessment of uptake, we have studied the influence of the number and the position of the methyl groups of IFA intracellular metabolism; 16-iodo-2-methyl-hexadecanoic (mono-alpha), 16-iodo-2,2-methyl hexadecanoic (di-alpha), 16-iodo-3-methyl-hexadecanoic (mono-beta), and 16-iodo-3,3-methyl-hexadecanoic (di-beta) acids were injected into the coronary arteries of isolated rat hearts. Intracellular analysis shows that the degradation of mono-alpha was always lower than that of IHA and the storage was always much higher. The differences between mono-beta and IHA were similar to those observed with mono-alpha, but were much more pronounced. With the two dimethylated IFAs there was an inhibition of both oxidation and esterification which led to an accumulation of free FAs in myocardial cells. In conclusion, mono-beta, di-alpha, and di-beta are potentially suitable for studying the cellular uptake of IFA since all of them, and particularly the dimethylated IFAs, have a low oxidation rate.  相似文献   

5.
To estimate the radiation dose of ingested 14C- (and 3H-) labelled fatty acids, we measured 14CO2 in samples of expired air in five subjects, and serum 14C activity in four subjects, over 4 weeks. These investigations showed that 25%–40% of ingested 14C-fatty acids were metabolized and expired as 14CO2 within 10 days after ingestion. The residue was expired with a calculated half-life of 493 days. Six days after ingestion of the radiolipids, radioactivity in serum was barely detectable. From these data of 14C-fatty acid metabolism, a total whole-body radiation of 20 mrem/Ci 14C, 8 mrem/Ci14C the first years, was calculated. The corresponding radiation dose for 3H-fatty acid was 2 mrem/Ci 3H and 1 mrem/Ci 3H respectively. Maximal organ-specific radiation (gonads and lungs) from the blood-borne radioactivity was 1 mrem/Ci of 14C-fatty acid.  相似文献   

6.
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.  相似文献   

7.
The characteristics of radiolabelled cholylglycyl-tyrosine (CGT), a recently synthesised bile acid, were studied. 125I-CGT-Na was found to have a short plasma half-life of 1.6±0.4 min in rats and 3.1±0.7 min in dogs. Biliary clearance studies showed the cumulative biliary output of the tracer over 20 min in rats to be 95.7% of the total dose administered, with a mean biliary transit time (50% retention time) of 4.0±0.1 min, i.e. similar to the biliary kinetics of taurocholate. 131I-CGT-Na proved to be satisfactory for hepatobiliary imaging in rats and dogs at doses of 35 Ci (1.3 MBq) in rats and 90 Ci (3.3 MBq) in dogs. Satisfactory hepatic images were also obtained in rats that had high bilirubin levels produced by obstruction or the recycling of bile. These results show that CGT has better pharmacokinetics than currently used hepatobiliary imaging agents, and that this new compound may be useful in scintigraphy even in the presence of jaundice.  相似文献   

8.
In our pursuit for liver functional diagnosis, development of bifunctional radiopharmaceutical containing iminodiacetic acid (IDA), as the technetium chelating site along with phthalein or fluorescein structure, the skeleton of BSP and Rose Bengal, long used for the assessment of liver function is considered. Among the various PC, PPC, TPC and calcein IDA derivatives commercially available,99mTc-PC (PC: 3,3-bis(N, N-dicarboxymethylaminomethyl)o-cresolphthalein) showed the highest hepatobiliary excretion. The functionality of the various technetium labeled phthalein and fluorescein IDA derivatives was evaluated by competitive BSP binding studies and by comparative binding with the hepatocyte specific protein, ligandin.  相似文献   

9.
It is recognized that iodine-123-labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123IBMIPP) slowly washes out of the myocardium. The mechanism for the washout was investigated in normal rat hearts by analyses of the subcellular distribution and lipid classes based on the BMIPP metabolism. Rat hearts were excised at 1–120 min after intravenous injection of123I-BMIPP. After counting the radioactivity, the hearts were digested with Nagarse and homogenized, and then fractionated into the cytosolic, mitochondrial, microsomal and crude nuclear fractions by centrifugations. The radioactivity of each fraction was counted, and the lipid classes were analysed by radio-thin-layer chromatographic and high-performance liquid chromatographic methods. The heart uptake of 1231-BMIPP was maximal at 5 min (6.81%±0.36% ID/g), and 41% of the radioactivity disappeared within 120 min. The myocardial radioactivity was immediately distributed into the cytosolic, mitochondrial, microsomal and crude nuclear fractions. The distribution (%) of each fraction was almost identical from 5 min through 120 min. The cytosolic fraction was always the major site of radioactivity deposition (60%), and the time-activity curve of the cytosolic fraction paralleled that of the whole heart throughout the 120-min study period. In the cytosolic fraction, most of the radioactivity was incorporated into the triglyceride class, and the rest was present in the free fatty acid, phospholipid (phosphatidylcholine) and diglyceride classes. In the mitochondrial fraction, the radioactivity was mostly incorporated into the phospholipid class (phosphatidylethanolamine), followed by free fatty acids. The final metabolite of123I-BMIPP,123I-p-iodophenylacetic acid (123I-PIPA), initially appeared in the mitochondrial fraction as early as 1 min, and subsequently in the cytosolic fraction at 5 min. Another intermediary metabolite,123I-p-iodophenyldodecanoic acid (123I-PIPC12), was found only in the mitochondrial fraction after 5 min. In conclusion, the slow washout kinetics of123I-BMIPP from the myocardium mainly reflects the turnover rate of the triglyceride pool in the cytosol. The BMIPP metabolism, i.e. initial -oxidation followed by subsequent cycles of -oxidation, was confirmed in vivo. The participation of the mitochondria in the metabolism was also proven.  相似文献   

10.
Radioiodine labelled 17-iodo-heptadecanoic acid (IHA) is used for non-invasive study of myocardial metabolism in coronary heart disease and cardiomyopathy. Yet in the interpretation of in vivo myocardial tracer kinetics, it is controversial whether the intracellular degradation of IHA or the removal of iodide across cellular membranes is the rate-limiting step in iodide release from the myocardium. In five patients undergoing coronary sinus catheterization, a mixture of about 40 kBq of [123I] NaI was injected into the left coronary artery. During the following 15-min period, frequent blood samples were taken from the aorta and the coronary sinus. In the aqueous phase of the venous blood, 14CO2 and inorganic 131I appeared nearly in parallel, with a peak time of 4–5 min. Moreover, as shown by the AV difference, there was no significant back diffusion of IHA and no significant non-specific deiodination detectable over the period of observation. There was myocardial retention of inorganic iodide (123I) injected into the left coronary artery. The data strongly support the premise that lipid turnover through -oxidation is the rate-limiting step in the externally measured release of iodide after IHA injection, provided that recirculating inorganic radioactive iodide is corrected for. In addition, 15 volunteers were studied using [11C]palmitic acid and [123I]IHA using PET and dynamic planar camera scintigraphy with iodide correction. There was no significant difference between the mean values of the elimination half-times, and also no significant correlation between half-times of both fatty acids for single individuals.  相似文献   

11.
In a case of primary hyperparathyroidism, a palpable nodule, at the base of the right lobe of the thyroid, proved cool during 99mTc scanning, but hot when scanned with radiocesium. The uptake of this tracer was higher than the uptake of 75Se-selenomethionine after suppression with T3.The authors discuss the possibility of cases of false-positive radiocesium uptake in extrathyroid nodules, and in particular, the use of this tracer for the detection of parathyroid adenoma by scanning.  相似文献   

12.
Radiolabelled 2-Cabomethoxy-3-(4-iodophenyl)tropane (-CIT) has been used in clinical studies for the imaging of dopamine and serotonin transporters with single-photon emission tomography (SPET). 2-Carbomethoxy-3-(4-iodophenyl)nortropane (nor--CIT) is a des-methyl analogue of -CIT, which in vitro has tenfold higher affinity (IC50=0.36 nM) to the serotonin transporter than -CIT (IC50=4.2 nM). Nor--CIT may thus be a useful radioligand for imaging of the serotonin transporter. In the present study iodine-125 and carbon-11 labelled nor--CIT were prepared for in vitro autoradiographic studies on post-mortem human brain cryosections and for in vivo positron emission tomography (PET) studies in Cynomolgus monkeys. Whole hemisphere autoradiography with [125I]nor--CIT demonstrated high binding in the striatum, the thalamus and cortical regions of the human brain. Addition of a high concentration (1 M) of citalopram inhibited binding in the thalamus and the neocortex, but not in the striatum. In PET studies with [11C]nor--CIT there was rapid uptake of radioactivity in the monkey brain (6% of injected dose at 15 min) and high accumulation of radioactivity in the striatum, thalamus and neocortex. Thalamus to cerebellum and cortex to cerebellum ratios were 2.5 and 1.8 at 60 min, respectively. The ratios obtained with [11C]nor--CIT were 20%–40% higher than those previously obtained with [11C]-CIT. Radioactivity in the thalamus and the neocortex but not in the striatum was displaceable with citalopram (5 mg/kg). In conclusion, nor--CIT binds to the serotonin transporter in the primate brain in vitro and in vivo and has potential for PET and SPET imaging of the serotonin transporter in human brain.  相似文献   

13.
Recently, many studies have drawn attention to the possibility of imaging estrogen-receptor-positive breast cancer with a high-affinity ligand such as 17-(16-[125I]iodo)-estradiol (I-E2). We tried to determine the most suitable time and dose for imaging with this compound, using uteri of mature Sprague-Dawley rats. Although the uptake of I-E2 in the target organ (uterus) reached its peak 1 h after subcutaneous injection, the ratio of uptake in the target organ to that in nontarget organs (lung and muscle) peaked at 4 h. We also found that this ratio decreased as the dose increased. The clearest image was available 4 h after the dose meeting the minimum requirement for imaging was administered. An imaging trial of dimethylbenzanthracene (DMBA)-induced mammary carcinoma is also demonstrated.  相似文献   

14.
In some 99mTc-iminodiacetic acid studies, separation of the gallbladder from the duodenum can be difficult, despite multiple views. When faced with this problem, we have had the patient ingest 250 cc of tap water. This ingestion clears the duodenum of activity and has allowed us to see the residual activity in the gallbladder. This waterida view may be a useful addition in difficult to interpret hepatobiliary studies.  相似文献   

15.
Zusammenfassung Es wird eine einfache gas-chromatographische Methode zur Bestimmung von 2,2-Diäthylallylacetamid beschrieben. Die Serumprobe wird mit gesättigter Ammoniumsulfatlösung versetzt und mit Chloroform extrahiert. Die organische Phase wird eingedampft, der Rückstand in Äthylacetat/Eisessig gelöst und in den Gaschromatographen injiziert. Der Variationskoeffizient für die Präzision in der Serie beträgt 8,5 %, die Wiederfindung 76 %, die Nachweisgrenze 3,2 mol/1. Der Extrakt kann auch zur Bestimmung anderer Schlafmittel benutzt werden. Die höchsten, bei schweren 2,2-Diäthylallylacetamid-Vergiftungen gemessenen Konzentrationen betrugen ü ber 700 mol/1.  相似文献   

16.
Zusammenfassung Die Interpretation von postmortalen Serumdigoxinspiegeln wird vor allem dadurch erschwert, daß mit einem präfinalen and postmortalen Anstieg der Digoxinkonzentration im Blut zu rechnen ist. Eriksson et al. (1984) dividierten die postmortal gemessenen Digoxinspiegel im Femoralvenenblut durch 1,5, um den postmortalen Anstieg des Serumdigoxinspiegels zu berüicksichtigen; nach Meinung dieser Autoren weisen postmortale Serumdigoxinspiegel, die nach Division durch 1,5 noch über dem therapeutischen Bereich liegen, auf eine Digoxinüberdosierung hin. Der diagnostische Wert des von Eriksson et al. (1984) vorgeschlagenen Korrekturfaktors wurde überprüft. In 56 Fällen mit dokumentierter Digoxin-Medikation wurde postmortal Femoralvenenblut asserviert und eine Serumdigoxinspiegelbestimmung durchgeführt. In keinem der untersuchten Fälle war klinisch eine Digoxin-Intoxikation diagnostiziert worden. 50% der gemessenen Werte lager oberhalb des therapeutischen Bereichs (0,7 ng/ml bis 2,2 ng/ml). Nach Division der gemessenen Werte durch 1,5 lagen noch immer ca. 20% über 2,2 ng/ml, der höchste korrigierte Wert betrug 4,44 ng/ml. Unter Berücksichtigung des Zeitraums zwischen letzter Gabe und Tod, der individuell unterschiedlichen Digitalisglykosidempfindlichkeit sowie der Komplexität präfinaler und postmortaler Verteilungsvorgänge wurde für unser Untersuchungskollektiv festgestellt, daß eine (unerkannte) Digoxinüberdosierung auch darn nicht wahrscheinlich war, wenn der postmortale Wert nach Division durch 1,5 noch über dem therapeutischen Bereich lag. Der vor Eriksson et al. (1984) vorgeschlagene Korrekturfaktor ist nur vor begrenztem diagnostischem Wert; die korrigierten Werte können allenfalls einen Hinweis darauf geben, in welchem Bereich sich die entsprechende antemortale Serumdigoxinkonzentration bewegt haben könnte. Vor allem korrigierte Werte, die nur wenig über dem therapeutischen Bereich liegen, können den Verdacht auf eine Digoxinüberdosierung nicht mit ausreichender Sicherheit stützen.Ausführliche Darstellung siehe Dissertation St. Ritz, Kiel, Dissertation eingereicht Sonderdruckanfragen an: S. Ritz  相似文献   

17.
Following receipt of fission product 99mTc-generators, results of radionuclide purity analysis, performed within 30 min after the first elution, demonstrated detectable levels of a contaminate radionuclide not previously reported. Gamma spectroscopy and half-life determinations confirmed the presence of 82Br. Bromine-82 activity, in eluates from the first elution of 30 generators, received weekly during a 7-month period, ranged from 0.22 Ci (8.235 kBq) to 0.67 Ci (24.68 kBq) per eluate. The ratio of 99Mo to 99mTc ranged from 0.13 nCi to 0.39 nCi per mCi 99mTc. The presence of 82Br in 99mTc-generator eluate resulted in falsely elevated 99Mo assay determinations using whole vial 99Mo assay procedures. For every 0.1 Ci 82Br present in 99mTc eluate the 99Mo assay results were elevated by 1 Ci. Gamma spectroscopy of eluates from additional elutions of these generators failed to detect the presence of 82Br demonstrating the displacement of monovalent bromine anions from the alumina column during the first elution.  相似文献   

18.
To accommodate the increasing need for [1-11C]fatty acids for use in routine medical studies and the large amounts of radioactivity required, a more advanced automated synthesis system for the preparation of [1-11C]fatty acids has been constructed. The synthesis of [1-11C]fatty acids has been completely automated using a new separation unit (isobaric Sepaltor) for the extraction procedure, which had caused some difficulties with automation. The yield of [1-11C]palmitic acid was 20–30 mCi, and that of 3-methyl [1-11C]heptadecanoic acid was 2–7 mCi. The time required for the synthesis was less than 30 min from the start of the 11CO2 trapping. This system has been used for more than 20 preparations of [1-11C]palmitic acid and more than 20 preparations of 3-methyl [1-11C]heptadecanoic acid.  相似文献   

19.
A biochemical concept is proposed for a radioiodinated fatty acid avoiding high iodine background in imaging studies of the myocardium. For this approach -(p-123I phenyl)-pentadecanoic acid is chosen and a method for synthesis and quality control described.  相似文献   

20.

Background

A radioactively labeled beta-methyl branched fatty acid analog,123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP), has been developed to probe regional myocardial fatty acid metabolism. However, the significance of BMIPP uptake in the myocardium remains unclear.

Methods and Results

To evaluate the significance of BMIPP uptake, single-photon emission computed tomography was performed 30 minutes after injection of BMIPP, and201Tl-labeled single-photon emission computed tomography was taken on a separate day in 10 patients. Findings of BMIPP and201Tl-labeled imaging were compared with the data obtained from positron emission tomography with11C-labeled palmitate. The BMIPP uptake (percent of maximum) was significantly correlated with the early uptake (percent) and delayed uptake (percent) of11C-labeled palmitate (r=0.659 andr=0.687, respectively) (p<0.01 each), whereas it was not significantly correlated with the residual fraction (r=0.205) or the clearance half-time of the early component (r=0.138) of11C-labeled palmitate as a marker of β-oxidation of the fatty acid.

Conclusions

These data indicate that, although the myocardial uptake of BMIPP may not directly reflect β-oxidation of fatty acids, its uptake may reflect both regional myocardial blood flow and fatty acid extraction.  相似文献   

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