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H J Machulla

Publications and source records attributed to H J Machulla.

35 records · Page 2Linked to original sources
PubMed1985

Metabolism of 15 (p 123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues.

The uptake and turnover of omega(p 123I iodophenyl-)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in the heart, lung, liver, kidneys, spleen, and skeletal muscle of rats. At 2 min post injection, a high cardiac uptake of 4.4% dose per gram had already been achieved; this was followed by a rapid, two-component, tracer clearance. The kinetics of tissue concentrations of labeled hydrophilic catabolites indicated a rapid oxidation of I-PPA and the subsequent washout of I-PPA catabolites from heart-muscle tissue. The fractional distribution of the labeled cardiac lipids compared favorably with previously reported values for 3H-oleic- or 14C-palmitic-acid-labeled myocardial lipids. Typical patterns of I-PPA metabolism were observed in tissues depending on primary fatty-acid oxidation, lipid metabolism regulation, or I-PPA-catabolite excretion. The tissue concentrations and kinetics of I-PPA and its metabolites in the heart muscle indicated that general pathways of cardiac-lipid metabolism are traced by this new gamma-emitting isotope-labeled radiopharmaceutical.

Animals↗
PubMed1985

Use of 3-fluoro-deoxyglucose for the assessment of cerebral perfusion and glucose transport. I. Theory.

A new model is described applying dynamic positron emission tomography (dPET) and 3-fluoro-deoxyglucose (3FDG) to the measurement of local cerebral perfusion and glucose transport across the blood-brain-barrier (BBB). The model takes advantage of 3FDG being practically not metabolized in brain and being transported back from tissue into the circulation. Simultaneous registration of tracer concentration in blood and tissue by dPET permits the in vivo determination of the Michaelis-Menten constant (K) and maximal velocity (V) for 3FDG and glucose transport across the BBB as well as the determination of local perfusion rate. Values obtained in normal cortex using this method were K = 6.3 mumol/g and V = 2.46 mumol/g min. Local perfusion rate ranged between 0.8 and 0.98 ml/min g.

Blood-Brain Barrier↗
PubMed1985

Use of 3-fluoro-deoxyglucose for the assessment of cerebral perfusion and glucose transport. II. Evaluation of patients undergoing EC-IC bypass surgery.

Dynamic positron emission tomography (dPET) and 3-fluoro-deoxy-glucose (3FDG) have been applied to the followup of selected patients undergoing extracranial-intracranial (EC-IC) bypass surgery. To determine glucose transport across the blood-brain-barrier and local perfusion rate a new mathematical model has been used. Immediately following EC-IC surgery, dPET shows an increase in perfusion of approx. 7 ml/min 100g over both the operated and the contralateral hemispheres indicative of reversal of interhemispheric steal. Followup studies show reduction of local perfusion rate combined with an improvement of glucose transport rates. This finding suggests improvement of cerebral metabolic capacity following improvement of perfusion suggestive of longterm beneficial effects of EC-IC bypass.

Blood-Brain Barrier↗
PubMed1984

15(p-[123I]Iodophenyl)pentadecanoic acid as tracer of lipid metabolism: comparison with [1-14C]palmitic acid in murine tissues.

Uptake and turnover of 15-(p-[123I]iodophenyl)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in heart, lung, liver, kidneys, and spleen and compared with that of [1-14C]palmitic acid (PA). High cardiac uptake of both I-PPA (4.4% dose/g) and PA (2.8% dose/g) was followed by a two-component tracer clearance. Kinetics of I-PPA were linked to those of PA in tissues with primary oxidation of free fatty acids or their preferential storage. Tissue lipids of all organs investigated were labeled concordantly by both tracers. Fractional distributions of PA and I-PPA incorporation in tissue lipids were significantly correlated. Thus general pathways of FFA tissue metabolism are traced by this radioiodinated free-fatty-acid analog. High-quality metabolic imaging of the heart is possible by means of I-PPA with conventional scintigraphic equipment or cross-sectional imaging with single photon emission computerized tomography facilities.

Animals↗
PubMed1984

Recent developments in the field of 123I-radiopharmaceuticals.

Due to its advantageous nuclear physical properties iodine-123 is an excellent label for radiopharmaceuticals very well suited for measurements by gamma-cameras and single-photon emission tomography. The development of 123I-radiopharmaceuticals should be based on a clear biochemical concept, reliable labelling procedures and careful pharmacokinetic studies in order to evaluate the physiological behaviour of the radioiodinated compounds being analogues of metabolic substrates. The development of 123I-labelled fatty acids and biogenic amines clearly proved the successful use of 123I for labelling compounds applied in medical diagnosis.

Amphetamines↗
PubMed1984

Relation of myocardial blood flow and initial cardiac uptake of 15-(p-123I-phenyl)-pentadecanoic acid in the canine heart.

In 8 pentobarbital-anesthetized mongrel dogs the correlation between regional myocardial blood flow (RMBF) and regional cardiac uptake of 15-(p-123I-phenyl)-pentadecanoic acid (IPPA) was determined. Three animals were studied under control conditions, in three dogs an acute ischemia was produced by LAD ligation, and two dogs were paced at 195 beats/min. RMBF values were 20-50 ml/min X 100 g in acutely ischemic myocardium. 90-120 ml/min X 100 g under normal conditions and 200-250 ml/min X 100 g during pacing-induced stimulation. Total cardiac uptake of IPPA was 4.5-6% of the injected dose. In normal and acutely ischemic myocardium a good correlation between RMBF and IPPA uptake was obtained. Under stimulated conditions only a moderate increase of IPPA accumulation was found. At RMBF values above 150-170 ml/min X 100 g an upper limit of IPPA uptake was observed and can be explained by limited diffusion or an increased utilization of alternative substrates.

Animals↗
PubMed1984

[123-I-labeled fatty acids for myocardial functional diagnosis].

For 17-123I-heptadecanoic acid (IHA) and 15-(para-123I-phenyl)-pentadecanoic acid (IPPA) the biochemical and pharmacokinetic results show a physiological behaviour similar to the normally occurring fatty acids. For the nuclear medical application both 123I-fatty acids are very well suited; they are fast and efficiently accumulated in the myocardium and, keeping the patient at rest, they allow to record scintigrams of the myocardium with a quality which is obtained with thallium 201 only under stress conditions of the patient. By sequential registration of the scintigrams time activity curves can be generated reflecting the regional in-vivo turnover of fatty acids in the myocardium. Thus in a non-invasive way it is possible to obtain differential informations of the myocardial function in-vivo.

Animals↗
PubMed1984

Cardiac metabolism of omega-(p-iodo-phenyl)-pentadecanoic acid: a gas-liquid chromatographic-mass spectrometric analysis.

The omega-(p-iodo-phenyl)-pentadecanoic acid (I-PPA) has been used successfully for the investigation of the cardiac metabolic activity and for the imaging of the myocardium (Machulla, H. J., M. Marsmann, and K. Dutschka. 1980. Eur. J. Nucl. Med. 5: 171-173). In the present study, the metabolic fate of I-PPA in the perfused rat heart was investigated. After application of I-PPA to the perfused rat heart, lipids were extracted, separated by thin-layer chromatography, and transesterified. The gas-liquid chromatographic-mass spectrometric (GLC-MS) analysis yielded the following results. Heart triglycerides contained 73% of the recovered I-PPA; only small amounts of unesterified I-PPA were found in the heart. This finding is in good agreement with the radioactivity distribution determined simultaneously. Three metabolites could be detected and characterized by GLC-MS: omega-(p-iodo-phenyl)-propionic acid, omega-(p-iodo-phenyl)-propenoic acid, and p-iodo-benzoic acid. These short chain metabolites were found only in the perfusion medium demonstrating that they are not enriched but rapidly eliminated from the perfused rat heart.

Animals↗
PubMed1984

Synthesis of, and animal experiments with, N-isopropyl-p-123I-iodo-amphetamine (IMP) and 18F-3-deoxy-3-fluoro-D-glucose (3-FDG) as tracers in brain and heart diagnostic studies.

For the investigation of brain functions 18F-3-deoxy-3-fluoro-D-glucose (3-FDG) and N-isopropyl-p-123I-iodo-amphetamine (IMP) were synthesized and the course of radioactivity measured in several organs of mice. The results can be summarized as follows: IMP is rapidly extracted from the blood and reaches a value of less than 1% g within the first 15 min; 123I-radioactivity in the lungs shows a maximum of 76%/g as soon as half a minute after injection and decreases with a concomitant increase in the liver and brain; The maximum 123I-uptake in the brain of 11%/g is reached after 30 min and levels off at a constant value of 10%/g; 30 min after injection the brain/blood ratio for IMP is about 14; The time course of 3-FDG in the brain has a maximum of 4.8%/g as soon as 5 min after injection and decreases to a constant value of 3%/g within 1 hr; and Accumulation of 18F- radioactivity in the heart reaches a maximum of 14%/g after 1 hr and is eliminated with a half-life of 300 min. Comparative clinical studies with 3-FDG and 3-0-11C-methyl-D-glucose (CMG) have shown that 3-FDG can be considered as a CMG-analogue and thus can be used for the in-vivo determination of local glucose perfusion and transport rates.

Amphetamines↗
PubMed1984

Cardiac metabolism of 15 (p-I-123 phenyl-) pentadecanoic acid after intracoronary tracer application.

Myocardial turnover of omega-(p123I-Phenyl-) pentadecanoic acid and release of its metabolites into the coronary sinus and peripheral blood has been studied in patients with coronary artery and valvular heart disease. After intracoronary tracer injection myocardial extraction fractions of 45-53% in control subjects were observed. In patients with coronary artery disease (CAD) normal to reduced values (34-61%) were established. Hydrophilic catabolites of I-PPA, probably p123I-benzoic and -hippuric acid as well as small amounts of the non-metabolized tracer were found in coronary sinus and peripheral blood. Myocardial tracer uptake and clearance patterns were clearly different in normal myocardium when compared to that obtained in patients with CAD. Thus, evaluation of myocardial I-PPA metabolism might provide a new diagnostic tool for assessment of integrity of the heart's muscular metabolic function.

Coronary Disease↗
PubMed1982

Assessment of regional myocardial uptake and metabolism of omega-(p-123I-phenyl) pentadecanoic acid with serial single-photon emission tomography.

The utility of myocardial imaging and assessment of regional myocardial metabolism of omega-(123I-paraphenyl-)pentadecanoic acid (I-PPA) by means of serial single-photon tomography is demonstrated in animal experiments. High quality cross sectional images of dog hearts with clear delineation of left ventricular walls are obtained. Myocardial infarcts are visualized as areas of deficient radioactivity uptake. I-PPA elimination from non-infarcted myocardial regions is significantly (p less than 0.001) prolonged when compared with unaffected controls. Hence, not only localized absence of uptake of free fatty acid by infarcted myocardium can be demonstrated with serial single-photon tomography but also general impairment of cardiac FFA-metabolism.

Animals↗
PubMed1980

Myocardial imaging and metabolic studies with [17-123I]iodoheptadecanoic acid.

After intravenous administration of the stearic acid analogue [17-123I]iodoheptadecanoic acid (I-123 HA), myocardial metabolism was studied in ten normal individuals, eight patients with coronary artery disease and three patients with congestive heart failure. High-quality images were obtained in sequential scintigraphy of I-123 metabolically bound in myocardial tissue. Infarcted zones as well as ischemic regions are indicated by reduced tracer uptake. Iodine-123 in the blood pool and interstitial space consists mainly of radioiodide that is liberated by fatty-acid metabolism and was corrected for. Using the proposed correction not only are the images improved but the uptake and elimination of the I-123 in the myocardial cells can be followed. The average disappearance half-time of I-123 HA from the myocardium of normal persons was 24 +/- 4.7 min. In patients with coronary artery disease significant differences between myocardial regions were observed.

Adult↗
PubMed1978

Comparative evaluation of fatty acids labeled with C-11, Cl-34m, Br-77, and I-123 for metabolic studies of the myocardium: concise communication.

Various long-chain fatty acids have been labeled with C-11, Cl-34m, Br-77, and I-123 and evaluated for their potential application in measuring myocardial metabolism in vivo. Comparative studies of the kinetics of accumulation and clearance from the heart muscle of mice indicate that the extraction of omega-halofatty acids is more efficient than that of alpha-halofatty acids. Among the omega-halofatty acids, the highest uptake is observed for the 17-iodoheptadecanoic acid, which shows an extraction behavior almost identical to that of [1-11C] palmitic acid, although with a higher radioactivity level in blood due to the release of free iodide.

Animals↗
PubMed1975

Production of short-lived radioisotopes for medical applications using high-energy reactions at JULIC.

The advantages of high energy nuclear reactions for the production of some special short-lived carrier-free radionuclides for allication in nuclear medicine are outlined. The routine production of 11C (T = 20.3 min), 123I (T = 13.3 h) and 28Mg (T = 21.1 h) at the Julich Isochronous Cyclotron JULIC via the 12C(p,pn) 11C-, 127I(d,6n) 123Xe(beta+, EC) 123I- and 27Al(alpha,3p) 28Mg-reaction, respectively, is described. Some areas of fast labelling and its applications are given.

Nuclear Medicine↗