The uptake of iodinated free fatty acids in the (ischemic) dog heart. Indications for a dual uptake mechanism.
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Animals↗
Biomedical subjects
G Westera
Publications and source records attributed to G Westera.
Myocardial scintigraphy with 123I-labelled heptadecanoic acid in patients with unstable angina pectoris.
Calculation of metabolic turnover rates with 123I-heptadecanoic acid (123I-HA) can detect regional myocardial ischaemia in patients with coronary artery disease. We have previously demonstrated different turnover rates in patients with stable angina compared with myocardial infarction. Twelve patients with unstable angina have now been studied: 8 patients showed imaging defects in 12 different myocardial regions and in 4 no defects were observed. Turnover rates were derived from time-activity curves and expressed in minutes half-time (t 1/2). All 12 regions with accumulation defects showed increased t 1/2 values (45.4 +/- 4.8 min) compared to normally perfused zones (29.1 +/- 3.6 min). The results suggest that the use of 123I-HA can identify ischaemic areas of myocardium in unstable angina and that the turnover of 123I-HA is different from that already established in the areas with infarction.
Angina Pectoris↗
Labelled bleomycin as a tumour-localizing agent. II. The effect of dose loading of the different forms of 57Cobalt-bleomycin A2, B2, and pepleomycin on the tissue distribution and tumour uptake in tumour-bearing rats.
The different forms of 57cobalt-bleomycin (57C0-blm) A2 and B2 as well as 57Co-pepleomycin (57Co-pep), were investigated in tumour-localizing properties of both forms of 57Co-blm are identical if 57Co-blm is injected as a bleomycin solution without carrier cobalt. Differences between the biological behaviour of the various cobalt complexes (which differ in ligand arrangement) were found if these complexes were injected together with inactive cobalt bleomycin complexes of the same form. In this case Co-blm B2 form I and Co-pep form I localize better than Co-blm b2 form II and Co-pep form II respectively. Such a decrease in uptake by the tumour, compared with form I, was not observed for Co-blm A2-II.
Absorption↗
Labeled bleomycin as a tumor localizing agent III. Selectivity of tumor tissue uptake of the different forms of [57Co] bleomycin A2 and B2.
The cell uptake of the different forms (I and II) of [57Co]bleomycin A2 and B2 was studied in a Rhabdomyosarcoma cell culture. The results show that the uptake of form I appears to be significantly higher than the uptake of form II. The evidence presented indicates that form I is formed in vivo as well as in vitro from form II by biotransformation. Transferrin stimulates the uptake of Co-bleomycin B2 form I only. As a result of trypsin treatment, it is suggested that form II binds only on the outer cell membrane and is not able to pass this membrane.
Animals↗
Different iron(II) complexes of bleomycin A2.
By 13C-nmr on iron-bleomycin preparations, an iron-bleomycin-CO complex is found that loses its CO upon standing, as demonstrated using 14CO. Iron-bleomycin, prepared without rigorous exclusion of oxygen, reacts with CO to a stable diamagnetic iron-bleomycin-CO complex.
Bleomycin↗
Demethylation and auto-oxidation of different cobalt-=bleomycin complexes.
Demethylation of Co-bleomycin A2 by heating yields three different complexes: form I and form II and "orange" Co-bleomycin-demethyl A2. These complexes can be separated by HPLC and show different 1H NMR spectra. Preparation of Co-bleomycin-demethyl A2 by chelation of bleomycin-demethyl A2 with cobalt yields a Co-bleomycin-demethyl A2, which is auto-oxidized into Co-bleomycin A1.
Bleomycin↗
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 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.
Animals↗
External detection of regional myocardial metabolism with radioiodinated hexadecenoic acid in the dog heart.
In a previous study we have demonstrated that terminally iodinated hexadecenoic acid (131I-HA) and Thallium-201 (201T1) are comparable in myocardial uptake and distribution in the ischemic dog heart (Westera et al. 1980). In the present study the potential value of 131I-HA was proved in determining regional myocardial metabolism in 19 dog experiments. In ten dogs, 131I-HA was administered 5 min after occlusion of a coronary artery (group II), in six dogs after a 90 min occlusion period (group III). Three dogs served as controls (group I). The turnover rates (t 1/2) of 131I-HA were calculated from mono-exponential time-activity curves, obtained by external detection over ischemic and normally perfused areas during a 30 min period after IV injection of 0.7-1.5 mCi 131I-HA. The t 1/2 values in ischemic regions were found to be significantly longer (group II, 25.1 +/- 2.6 min; group III, 22.6 +/- 1.8 min) than in non-ischemic areas (group II, 12.5 +/- 1.8 min; group III, 14.2 +/- 1.4 min). The t 1/2 values in the control dogs (group I, 13.4 +/- 1.4 min) were not significantly different from the turnover rates in the non-ischemic areas of the occluded hearts. We conclude that the study of turnover rates of radioiodinated free fatty acids allows the determination of regional myocardial metabolism and offers a means to distinguish normally perfused from ischemic myocardial tissue.
Animals↗
Dynamic myocardial scintigraphy with 123I-labeled free fatty acids in patients with myocardial infarction.
We have already shown that myocardial imaging properties of radio-iodinated long-chain free fatty acids (123I-FFA) and thallium 201 (201TI) are comparable in detecting areas of inadequate myocardial perfusion (van der Wall et al. 1980). Besides confirming our earlier observations, the present study tests the potential of 123I-FFA, hexadecenoic acid (123I-16-ha), and heptadecanoic acid (123I-17-H degree A), in assessing regional myocardial metabolism in 30 patients within a week of proven myocardial infarction. The clearance rates (t1/2) of FFA were estimated from mono-exponential time-activity curves, obtained by external detection over infarcted and normally perfused areas during a 30-min period after IV administration of 3-5 mCi 123I-16-HA or 123I-17-H degree A. Six normal subjects served as controls. The t1/2 values in the infarcted areas were found to be significantly lower (18.5 +/- 2.1 min; mean +/- SD, with 123I-16-HA and 16.8 +/- 3.5 min with 123I-17-H degree A) than in non-infarcted areas (34.0 +/- 8.4 min with 123I-16-HA and 34.8 +/- 7.7 with 123I-17-H degree A). The t1/2 values in the control group (27.5 +/- 3.0 min with 123I-17-H degree A) were not significantly different from values found in non-infacted areas in the patient group. Our findings of faster FFA turn-over rates in infarcted tissue are in contrast to previous studies, which have shown prolonged turn-over rates in reversibly ischaemic myocardiu. We conclude that the study of turn-over rates of FFA provides a means to distinguish normally perfused, reversibly ischaemic and irreversibly ischaemic myocardium.
Adult↗
Metabolic myocardial imaging with 123I-labeled heptadecanoic acid in patients with angina pectoris.
The potential value of 123I-heptadecanoic acid (123I-H degree A) in myocardial scintigraphy has recently been assessed in patients with acute myocardial infarction (AMI) by studying regional myocardial metabolism (Van der Wall et al. 1981 a). To determine the metabolic behavior of 123I-H degree A in patients with stable angina pectoris (AP) as well, 30 patients with AP were included in this study: 18 patients were exercised and 12 patients were studied at rest. Regional myocardial metabolism was evaluated by generating background subtracted time-activity curves, acquired by external detection over normally perfused and ischemic regions during a 30-min period after intravenous injection of 123I-H degree A. Following monoexponential curve-fitting, clearance rates were measured representing turnover rate (T1/2) of 123I-H degree A. The exercise group showed prolonged T1/2 values of 46.7 +/- 7.1 min (mean +/- SD) in ischemic regions and 28.7 +/- 3.6 min in normally perfused regions. The group at rest did not reveal any scintigraphic abnormalities and showed normal T1/2 values in all myocardial regions (29.1 +/- 4.7 min). Our observations of prolonged turnover rates in ischemic areas differ from the results of our recent study in patients with AMI, which demonstrated fast turnover rates in infarcted tissue. These data imply that 123I-H degree A permits the study of myocardial metabolism in patients with AP and the discrimination of normally perfused, reversibly ischemic (AP) and irreversibly ischemic (AMI) myocardium.
Adult↗
The synthesis of some 11C-labelled antiepileptic drugs with potential utility as radiopharmaceuticals: hydantoins and barbiturates.
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Anticonvulsants↗
I-123 labeled hexadecenoic acid in comparison with Thallium-201 for myocardial imaging in coronary heart disease. A preliminary study.
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.
Adult↗
A comparison between terminally radioiodinated hexadecenoic acid (I-HA) and 201Tl-thallium chloride in the dog heart. Implications for the use of I-HA for myocardial imaging.
The regional myocardial distribution of 131I-16-iodo-9-hexadecenoic acid (131I-HA) and 201Tl-thallium chloride (201TlCl) was determined in normal dogs and after occlusion of a coronary artery. The uptake of 131I-HA was about 20% lower than that of 201TlCl but the ratio 201Tl/131I was the same for the whole myocardium within narrow limits for normal as well as infarcted tissue. The potential of 123I-HA as a radiopharmaceutical for diagnosis of myocardial defects is discussed.
Animals↗
The effect of dose loading and of double labelling with 57Co and 125I on the tissue distribution in animals.
Dose loading effects upon the performance of 57Co-bleomycin as a tumor localizing agent have been investigated in Rhabdomyosarcoma bearing Wag/Ry rats. The addition of non-radioactively labelled Co-bleomycin increased the relative uptake of 57Co-bleomycin in rapid growing tumors, but the addition of non-chelated bleomycin had no influence at all. In our experimental system, iodinated bleomycin generally labelled by reaction with ICl, was found to be an unsatisfactory tumor localizing agent. In order to combine the useful localizing properties of Co-bleomycin with the qualified detection properties of some iodine isotopes, we attempted to prepare bleomycin doubly labelled with Co and I. However, we were unable to prepare 57Co-125I-bleomycin by general labelling with ICl. This result indicates that both labels need the imidazole ring for the formation of a stable, labelled bleomycin.
Animals↗
Synthesis and electrophysiological studies of a novel epibatidine analogue.
The new epibatidine analogue exo-2-(2-pyridyl)-7-azabicyclo[2.2.1]heptane (2PABH) was synthesised. Separation of enantiomers was performed on chiral HPLC chromatography in polar-organic phase mode at 0 degree C. Enantiomeric purity was greater than 99.8%ee for the (-)- and 90.5%ee for the (+)-enantiomer respectively. Optical rotation was determined to be [alpha]23D = +/- 13 degrees. Electrophysiological studies of 2PABH were carried out on alpha 4 beta 2, alpha 3 beta 4 and alpha 7 nAChR subtypes cloned from rat and reconstituted in Xenopus oocytes. Both enantiomers could not significantly activate the heteromeric subtypes. The homomeric alpha 7 nAChR displays a high sensitivity only towards (-)-2PABH. The EC50 for (-)-2PABH and ACh were determined (32.5 +/- 9.5 microM, 137.3 +/- 16.5 microM). (-)-2PABH was shown to be a partial agonist (80% of ACh). Thus the efficacy of 2PABH differs markedly from that of epibatidine. The intramolecular N-N-distance and the spatial pyridine nitrogen orientation play a central role in nAChR recognition.
Animals↗