W. den Hollander

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.

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.

Radioimmunotargeting in ovarian carcinoma patients with indium‐111 labeled monoclonal antibody OV‐TL 3 F(ab′)2: pharmacokinetics, tissue distribution, and tumor imaging

Safety and feasibility of tumor targeting with radiolabeled monoclonal antibodies was studied in 28 patients suspected of having ovarian carcinoma, after i.v. administration of 1 mg F(ab′)2 fragments of the murine monoclonal antibody OV-TL 3, labeled with 150 MBq Indium-111. There were no adverse reactions, hematological and biochemical serum parameters were stable. In one patient a (subclinical) HAMA-response was found. Plasma clearance of the immunoconjugate was biphasic with half lives of t½}α = 1.4±0.8 h and t½}β = 25.1±3.7 h, resulting in an optimal time period for immunoscintigraphy at 24–48 h after administration. In 20 patients, undergoing extensive explorative surgery, a total of 271 samples of tumorous and normal tissues were analyzed for radiolabel uptake and tumor presence. The mean uptake in tumor deposits was 5.6 times (range 2.2–19.3) as high as the uptake in normal tissues (fat, peritoneum, muscle, skin). The diagnostic accuracy of immunosctigraphy was compared with that obtained with computer tomography, magnetic resonance imaging, ultrasonography and physical examination. While pelvic localizations were equally well detected by all methods, 48% of the abdominally located tumor deposits were correctly diagnosed by immunoscintigraphy, with only 12% detected by ultrasonography, 8% by CT-scanning and physical examination, and 6% by MRI. Immunoscintigraphy has potential as a diagnostic tool in ovarian cancer patients and biolocalization results justify further research into the therapeutic application of labeled monoclonal antibodies.

The elimination rate of 123I-heptadecanoic acid after intracoronary and intravenous administration

When calculating the elimination rate of radioactivity after the administration of radioiodinated heptadecanoic acid (123I-HDA), background correction is necessary due to the high level of background activity. In the present study, the subtraction method of Freundlieb et al. was investigated on validity. This was done by comparing the half-time values of the elimination rate after intravenous (i.v.) and intracoronary (i.c.) injection. In the latter case, no background correction was necessary. Six patients underoging cardiac catheterization were studied. Scintigraphy was performed after the injection of 123I-HDA into the left coronary artery and after i.v. injection. Half-time values were calculated from regions of interest drawn over myocardium perfused by the left-anterior descending branch (LAD) and the left circumflex artery (LCX). In the LAD region, the mean half-time value in the i.c. study was 22 min, while in the corrected i.v. study, the mean value was 27 min. In the LCX region, the half-time values were 24 and 33 min, respectively. The background-subtraction procedure proposed by Freundlieb et al. for i.v.-injected 123I-HDA ss incomplete, as it resulted in half-time values that were higher than those of the i.c. study.

Hepatic 123I-insulin binding kinetics in non-insulin-dependent (Type 2) diabetic patients after i.v. bolus administration

Insulin binding kinetics in the liver were studied in non insulin dependent (Type 2) diabetic patients, by i.v. bolus administration of 123I-insulin. Eight Type 2 diabetic patients were compared with six male volunteers. Uptake of 123I-insulin by liver and kidneys was measured by dynamic scintigraphy with a gamma camera during 30 min. Images of liver and kidneys appeared within 2–3 min after administration of 123I-insulin at a dose of 1 mCi (37 MBq). Peak radioactivity for the liver was found 7.5±0.2 and 6.9±0.3 min after injection for the healthy and the diabetic subjects, respectively (N.S.). The percentage 123I-insulin hepatic uptake was not significantly different for the diabetic and the healthy subjects.Although a large variation exists for maximal uptake of radioactivity within both groups, the data suggest that binding differences in the liver in Type 2 diabetic patients, as compared to healthy subjects, may not account for hepatic insulin resistance.

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.

Kinetics and dosimetry of iodine-131-labelled antibody fragments after local administration in patients with rectal cancer

In 11 patients with rectal cancer, a mixture of F(ab′)2 fragments of anti-carcinoembryonic antigen and anti-CA 19.9 labelled with a diagnostic dose of iodine-131 (3–10 MBq) was administered submucosally around the tumour. In this study, the local kinetics in and the dose to the rectal wall, the whole body kinetics and the effective dose equivalent are presented. The early disappearance of the activity from the injection spot was characterized by a T1/2 of 21 h. Initially, about 50% of the plasma activity was due to free 131I. After 4 h, the plasma activity was almost completely protein bound (86%). Maximum plasma activity was observed after the 2nd day. From 72 h p.i., the plasma activity decreased with a T1/2 of 53 h. In the first 24 h, 14% of the injected dose was excreted in the urine and within 4 days about half of the administered activity. The absorbed radiation dose to the rectal wall was estimated to be 0.2 Gy/MBq, presuming a 20 cm3 distribution volume. The dose to the bone marrow was 0.2 mGy/MBq or 0.4 mGy/MBq, assuming a homogeneous tracer distribution or equal blood and bone marrow activity concentrations, respectively. The effective dose equivalent is 1.9 mSv/MBq, mainly determined by the dose to the rectal wall and to a lesser extent by the dose to the remaining body. Postulating comparable kinetics, 123I- or 111In- or 99mTc-labelled fragments would result in 4-25-fold lower effective dose equivalents. We conclude that the theoretical advantages of the local administration of 131I-labelled antibodies for diagnostic purposes in patients with rectal cancer are not limited by our dosimetric data. Nevertheless, we advocate the use of other radiolabels with more appropriate imaging qualities and probably a lower radiation burden.