F. Helus

Uptake and turnover of L-(13N)-glutamate in the normal human heart and in patients with coronary artery disease

L-(13N)-glutamate (4–8 mCi) was administered IV to 27 patients with coronary artery disease and to 12 control subjects.Quantitative whole body imaging of the 13N label was performed in 31 individuals at different time intervals following the injection. Initial uptake of the total myocardium was estimated to be 5.0±0.88% of the dose. Standardized areas of reduced size on the projection plane contained 2.38±0.41% of the total dose in control subjects and 2.67±0.49% in coronary patients. Subsequent imaging exhibited significant differences in the dynamic behavior of both groups: 13N activity loss within 10 min was 3.2±4.2% of the initial value in control subjects and 16.0±9.8% in coronary patients. In individual cases a high myocardial accumulation of the 13N label was observed in regions of reduced 201Tl uptake. The findings are explained by an augmented extraction efficiency in cases of flow reduction.Glutamate utilization may be involved in metabolic adaptations of the myocardium to chronic or repetitive ischemia and may be worthy of further investigation by positron emission tomography.

Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia.

The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium.

Selective drug-induced reduction of blood flow in tumor transplants

The effect of a calcium antagonist and a physiologic amine on tumor and muscle perfusion was investigated with the aim of improving the preconditions for external hyperthermia treatment of cancer. Nisoldipine (0.04-4.0 mg/kg) and 5-hydroxy tryptamine (5-HT) (0.2-8.0 mg/kg) were administered i.p. in Sprague-Dawley rats bearing Walker 256 carcinoma, Yoshida sarcoma, or a homologous tumor transplant derived from a spontaneous leiomyosarcoma of the uterus. At the maximum dosage used, nisoldipine injection caused a decrease of the regional washout rate of Xenon-133 of 63 +/- 8% (SEM) in the Walker carcinoma and an increase of 80 +/- 41% in the muscle of the hind leg. 5-HT (8 mg/kg) caused a drop of 79 +/- 29% in the Walker carcinoma and only a slight fall of the washout rate in muscle of 14 +/- 4.8%. Tumor-to-muscle uptake ratios of 11C-butanol fell from 5.63 +/- 1.98 to 3.32 +/- 1.21, and from 5.3 +/- 0.56 to 2.98 +/- 0.30, after injection of 0.2 mg/kg nisoldipine and 4 mg/kg 5-HT, respectively. Similar reaction patterns and percentage changes were observed in different tumor lines at constant doses of 0.2 mg/kg nisoldipine and 4 mg/kg 5-HT. Both drugs representing two different rationales of vasomotor action were able to reduce blood flow specifically in transplanted tumors; nisoldipine increased muscle blood flow and decreased arterial blood pressure, whereas 5-HT acted without substantial systemic effects.

Kr-81m for determination of right ventricular ejection fraction (RVEF)

A 10–12 mCi 81Rb→81mKr generator was connected to a specially designed short-period infusion set, to produce an equilibrium activity distribution in the right heart. This procedure was tested in 25 individuals to calculate the right ventricular ejection fraction (RVEF). On average 30 heart cycles were analyzed per study. No background activity from the left heart was visualized because of the radionuclide exhalation. The background from the lungs could be neglected, which is partially due to the ultrashort half-life of the nuclide (t1/2=13s). Thus, an easy automatic procedure can be applied to delineate the ventricle and to calculate the RVEF. The data showed excellent reproducibility, when investigations were repeated. The method would benefit from use of higher activity generators.

11C-Butanol for imaging of the blood-flow distribution in tumor-bearing animals

Abstract1-11C-n-Butanol produced semiatomatically using a cyclotron was employed to investigate the whole-body distribution and kinetics of the label of this compound. Following the administration of 11C-butanol into the aorta of two dogs, more than 80% of the activity was cleared from the blood within 1 min. The activity distribution mirrored the cardiac output distribution as determined using 121I microspheres. Within 25 min p.i., a significant release of decay-corrected activity was only observed for the liver, spleen, and kidneys. Muscle and whole-body activity showed constant levels during this period. In 45 tumor transplants from rats, the dynamic behavior of the label was studied. The tissue retention of activity following injection into the a. femoralis was approximately 100% during the 1st 15 s for both tumor and muscle (n=6). The activity release by tumors during the 1st 10 min after intra-aortic injection was 18%±4.5% (n=39; decay corrected). In five different tumor lines (n=10), the initial 11C-butanol uptake was related to that of muscle, and the results were correlated with the tumor-to-muscle retention of 121I-microspheres (r =0.89). In 17 tumors, the correlation between 11C-butanol uptake and the washout rate of 133Xe resulted in a correlation coefficient of 0.96. Tumor-to-muscle uptake ratios could be equally determined using intra-aortic and intravenous injection, as evaluated by intraindividual comparison in 12 rats (y=0.01+0.98x;r=0.98). 11C-Butanol appears to be an appropriate radiotracer for the assessment of blood supply to malignant tumors relative to muscle.

Routine production of38K for medical use

A method for a simple and fast production of38K for medical use has been developed. Different target materials have been tested, yield of38K and contaminants examined and chemical procedure and target system developed.

Tumour uptake of radiolabelled pyrimidine bases and pyrimidine nucleosides in animal models—IV. 2′-123I-iodo-2′-deoxyuridine

Iodine-123 was produced via the 124Te(p,2n)123I reaction by irradiating an enriched TeO2 target, using the DKFZ Heidelberg compact cyclotron. Radioiodine recovered from the target by sublimation was exchanged into carrier NaI, and reacted with 2,2′-anhydrouridine in dioxane and catalytic amounts of trifluoroacetic acid for 25 min at 135°C, to produce 2′-123I-iodo-2′-deoxyruridine. Radiochemical yields were as high as 84% with specific activities estimated at 17 Ci mmol−1. Tissue distribution and excretion studies after i.v. injection of 2′123I-iodo-2′-deoxyuridine into Wistar rats bearing Walker 256 carcinomas indicated limited tissue uptake and rapid urinary excretion. Only thyroid, kidneys, stomach and liver accumulated radioactivity. 90% of the i.v. dose was excreted in the urine, with 39% of the dose present as unchanged 2′-123I-iodo-2′-deoxyuridine.

Experiences in the routine production of123I via the124Te(p, 2n)123I reaction with a low energy cyclotron

This paper deals with the results and experimental observations obtained in routine production of123I via124Te(p, 2n)123I reaction, using the low energy cyclotron (protons, Emax=22 MeV) at the German Cancer Research Center in Heidelberg. The reaction was studied during the past 4 years using124TeO2 targets with various levels of enrichment. The purpose of the study was to determine which target material provided the highest quality and most economical production of123I. A viable routine production was defined as one in which123I could be conveniently and reproducably prepared in reasonable purity while maintaining a low cost for the entire process. Different methods of sublimation of123I activity from the124TeO2 target were examined to determine the optimal conditions for recovery of radioactivity and recycling of target material. A rapid method is described which permits quantitative separation of123I while allowing only a negligible loss of124TeO2.

Liquid scintillation counting of radionuclides emitting high-energy beta radiation

Liquid scintillation counting of radionuclides emitting beta radiation with Emax>2 MeV has been investigated. Fluor volume effects were similar to those for low energy beta radiation, and pulse height spectra broadened in a predictable manner with no pulse clipping up to 4.913 MeV. Large changes in sample channels ratio due to color quenching resulted in progressively smaller losses of counting efficiency as beta energy increased. Counting efficiences were estimated to be near 100 percent for34Clm,36Cl,32P and38Cl. Cerenkov counting of38Cl by liquid scintillation counter was volume dependent for both counting efficiency and pulse height spectrum. Counting efficiencies for34Clm,36Cl,32P and38Cl were estimated to be 57.0, 7.5, 42.7 and 66.3%, respectively. Pulse height spectra were shifted to greater pulse heights as a function of beta Emax, supporting the possibility of energy discrimination for beta emitters by Cerenkov pulse height spectrum analysis. The advantage of singles Cerenkov counting over coincidence Cerenkov counting was greatest for36Cl and least for38Cl; this advantage was amplified more for samples of36Cl which had been color quenched than for similarly quenched samples of38Cl or32P.

Contribution to cyclotron targetry. II: Testing of teh target construction materials for 18F production via 20Ne(d, α)18F, recovery of 18F from various metal surfaces

In a previous article1 we reported results on the distribution of18F activity in the gas target. The present paper continues to report on experimental studies of physicochemical effects involved in the20Ne(d, α)18F reaction, with the aim to improve the recovery of18F in both chemical forms i.e.18Fe−F2 and18F−F− from the target, without adding fluorine carrier. The choice of optimum target construction material is a very important factor for achieving a high extraction rate and high specific activity of the product. Recovery and desorption of the18F-activity from the surfaces of various metal foils in the liquid and gas phases have been investigated. This study is of interest from both the practical and theoretical point of view.