G. Westera

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 (201Tl) 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-HoA), 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-HoA. Six normal subjects served as controls. The t1/2 values in the infarcted areas were found to be significantly lower (18.5±2.5 min; mean±SD, with 123I-16-HA and 16.8±3.5 min with 123I-17-HoA) than in noninfarcted areas (34.0±8.4 min with 123I-16-HA and 34.8±7.7 with 123I-17-HoA). The t1/2 values in the control group (27.5±3.0 min with 123I-17-HoA) were not significantly different from values found in noninfarcted 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 myocardium. We coclude that the study of turn-over rates of FFA provides a means to distinguish normally perfused, reversibly ischaemic and irreversibly ischaemic myocardium.

Metabolic myocardial imaging with 123I-labeled heptadecanoic acid in patients with angina pectoris

The potential value of 123I-heptadecanoic acid (123I-HoA) 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-HoA 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-HoA. Following monoexponential curve-fitting, clearance rates were measured representing turnover rate (T1/2) of 123I-HoA.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-HoA permits the study of myocardial metabolism in patients with AP and the discrimination of normally perfused, reversibly ischemic (AP) and irreversibly ischemic (AMI) myocardium.

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.

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

To clarify the metabolic fate of radioiodinated heptadecanoic acid in myocardium, the time course and distribution of the radioactivity over 131I-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 131I-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 radioactivity was free iodide, and its curve paralleled the curve of the total radioactivity. As early as the first minute 131I-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, 131I-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 beta-oxidation rate as previously supposed.

The synthesis of some 11C-labelled antiepileptic drugs with potential utility as radiopharmaceuticals: Hydantoins and barbiturates

Abstract 11 C-labelled phenytoin and 5-ethyl-5-phenyl hyandantoin were prepared using 11 COCl 2 as the starting material. 11 C-urea was used to produce 11 -phenobarbital and 11 C-barbital. The methods developed are suitable for automation in a lead shielded cell.

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 (201Tl) 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 (t1/2) 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 t1/2 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 nonischemic areas (group II, 12.5±1.8 min; group III, 14.2±1.4 min). The t1/2 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.

A 13C nmr and esr study on the structure of the different forms of the cobalt-bleomycin A2 complex

Abstract 13 C nmr and esr spectra have been recorded from oxygenated cobalt-bleomycin A 2 . It appears that (a) in oxygenated cobalt-bleomycin all the cobalt is in the Co 3+ oxidation state, (b) the 13 C nmr data indicate a structure of the Co-bleomycin complex in which the nitrogens of the pyrimidine, the imidazole, and the secondary and primary amine of the diaminopropanoic amide are involved as planar equatorial ligands, and (c) free bleomycin forms a “dimer” with Co-bleomycin.

A u.v.-induced on-line synthesis of 11C-phosgene and the preparation of some of its derivatives

The on-line preparation of 11C-phosgene by the U.V.-induced reaction of 11CO with Cl2 is described. The versatility of this compound as a starting material in 11C chemistry is shown by the easy formation of 11C-labelled ethyl chloroformate, diethyl carbonate, ethyl carbamate and N,N′-diphenyl urea.

Different forms of the cobalt-bleomycin A2 complex

Abstract Chromatographic analysis of Co-bleomycin on CM Sephadex C25 or silica shows that known components like bleomycin A 2 , B 2 , and A 1 can be separated into two forms. We observed an equilibrium between both forms and saw that the addition of certain salts influences the transition of one form into the other. A reaction scheme is suggested in which a different occupation of the sixth binding site of cobalt is correlated with the different forms observed. These different complexes may be an intramolecular adduct of the carbamoyl moiety of bleomycin, an external carboxylate adduct or an oxygen or hydroxyl adduct.

Radioiodinated o-iodobenzoic acid as impurity in Hippuran preparations

Some factors determininghe presence of labelled o-iodobenzoic acid in preparations of Hippuran have been studied. Labelling procedures resulting in low o-iodobenzoic acid contents are presented.