D. de Bartolo

A methodology for biokinetic studies using stable isotopes: Results of repeated molybdenum investigations on a healthy volunteer

A method for biokinetic studies in humans using stable isotopes is presented. The technique is based on double tracer administration and on proton activation as the analytical method. As an application, the results of investigations on molybdenum metabolism in humans are reported. The contents of 95Mo and 96Mo in biological samples were determined by inducing (p,n) reactions and by analysing the gamma-rays emitted by the radioactive products. The minimum detectable quantity was 2 ng/mL plasma for both Mo isotopes. Four investigations on molybdenum metabolism were performed on a healthy volunteer subject in the course of 3 yr. Two absorption studies with different amounts of tracers in aqueous solution were performed by giving 96Mo orally and 95Mo intravenously. Two investigations were performed with single oral administration of 96Mo in aqueous solution and of a 96Mo solution mixed with an infant formula respectively. The stability with time of the biokinetic parameters was tested. The fractional absorption values measured in this volunteer were 0.84, 0.98 and 0.95 for three studies with Mo in HCl and 0.51 for a single study with Mo administered in an infant formula, these data are discussed.

Proton nuclear activation in stable tracer technique for ruthenium metabolism studies

Abstract A methodology is presented, based on proton nuclear activation (PNA), for the contemporary determination of two stable isotopes of ruthenium in biological samples. This technique can be successfully applied in studying the biokinetics of oligoelements, avoiding radiation hazards. On the basis of the possible proton-induced nuclear reactions and the decay characteristics of radioactive products, (p, n) reactions on 99 Ru and 101 Ru resulted to be the most convenient. The minimum detectable quantities resulted to be 15 and 3 ng/ml of plasma respectively. Ru fractional intestinal absorption in an experimental animal was determined, as a feasibility test for applications to humans. Following double tracer technique, one male rabbit was orally given 1 mg of 99 Ru and was injected 78 μg of 101 Ru. Eleven blood samples were drawn within 300 min after administration. Concentrations in plasma samples of intravenously and orally given Ru tracers are reported, as a function of time after administration. Fractional intestinal absorption was determined from concentrations of both isotopes, using the convolution integral technique. A Ru intestinal absorption of (5.5 ± 0.8)% within 300 min from the oral administration was obtained. The results show the effectiveness of this methodology and its applicability for future investigations in humans.

Molybdenum metabolism studied by means of stable tracers.

An investigation on molybdenum metabolism by administration of molybdenum stable isotopes was performed. Fractional intestinal absorption was determined in animals by the double tracer technique. The investigated subjects were given an enriched solution of Mo-96 orally and, a few minutes later, an enriched solution of Mo-95 intravenously. Blood samples were drawn at different times following the tracer administration. The Mo-95 and Mo-96 contents in plasma samples were determined by proton nuclear activation. The described methodology offers a means for the study of molybdenum metabolism in humans without radiation risk.

Intestinal absorption of tellurium studied with stable tracers

An investigation on tellurium metabolism by administration of stable tellurium isotopes124Te and126Te has been performed. Fractional intestinal absorption was determined in rabbits by the double tracer technique. The investigated subjects were given an enriched solution of one tellurium isotope orally and a few minutes later an enriched solution of the other isotope intravenously. The124Te and126Te contents in plasma samples were determined by proton nuclear activation. The methodology described offers a means to study tellurium metabolism in humans without radiation risk.

Response to a single oral test of molybdenum stable isotopes for absorption studies in humans

Two volunteer subjects were given orally enriched solutions of Mo-95 and Mo-96 respectively. Blood samples were drawn at various times following the tracer administration. The Mo-95 and Mo-96 content in plasma samples was determined by proton nuclear activation and the response to the single oral test of enriched stable molybdenum isotopes was determined. Assuming a simple two-open-compartment model where the first compartment is the gastrointestinal tract and the other is the plasma, an indicative value of the fractional intestinal absorption for the two subjects is given. The feasibility of direct quantitative measurements of Mo intestinal absorption by the double-tracer technique, using stable tracers, is evidenced.

Proton, Photon and Neutron Activation Analysis for the Determination of Stable Isotopes of Gadolinium in Human Blood Plasma

The biokinetics of radioactive substances can be studied using stable tracers. For the highly radiotoxic actinides, for which no stable isotopes are available as tracers, the use of stable isotopes of lanthanides as chemically related surrogates has been suggested. In this work, the possibility of using activation analysis with protons, photons, or thermal neutrons for the determination of single stable isotopes of gadolinium in biological samples has been tested. All the techniques show very good linearity response, and may be considered as complementary. Whereas activation analysis with protons is recommendable for the simultaneous determination of two different isotopes, neutron and photon (gamma) activation analysis should be chosen whenever a better sensitivity or simplicity of the analysis is required.

Irradiation chamber for the simultaneous nuclear activation of several targets

Abstract In this work an irradiation chamber, used for simultaneous proton activation of several samples in the same experimental conditions, is described, together with its refrigerating system. After a brief technical representation, a rough approach to the thermal behaviour of the whole system is made, in order to evaluate the maximum temperatures reached by the device and by the samples. Experimental measures are in good agreement with calculated values.

Stable and radioactive tracers in Ru biokinetic studies

The feasibility of ruthenium metabolism studies by stable tracer administration, with a methodology based on proton nuclear activation, is presented. In order to test that the amount of stable tracer administered does not perturb significantly the mechanism investigated, a series of comparative experiments with administration of both radioactive and stable tracers has been performed on animals. As the most critical pathway seems to be the intravenous injection, four male rabbits were given an intravenous injection of radioactive106Ru. Successively, the rabbits were given either a further injection of radioactive106Ru or injection of different quantities of natural Ru. The activity of106Ru and the concentration of natural Ru were measured in plasma samples withdrawn at different time intervals from the injections and the results were compared. Some biokinetic parameters and tissue distribution of Ru in rabbits were determined.

Use of charged particle activation as an analytical technique in the biological field

Some applications of Charged Particle Activation Analysis (CPAA) in the biological field are presented. This technique has been used frequently for the analysis of the light elements which are inaccessible to neutron activation analysis (NAA), but it is especially effective in the detection of medium-heavy trace elements and there is increasing interest in its employment in biological and medical fields. CPAA enables the identification and simultaneous quantification of different isotopes of the same element. Recent applications show that it can be used as a reference method in stable isotope determination for biokinetic studies of selected elements in complex organic matrices such as blood plasma.

Use of cyclotrons for trace element analysis in biological samples and related metabolism studies

Abstract In this work metabolic studies based on proton nuclear activation (PNA) are described. For such kind of experiments a very high sensitivity in concentration determination of adequate tracers in biological tissues is needed and the contemporary use of more than one isotope of some element is often necessary. Moreover the use of radioactive tracers is normally forbidden in healthy persons. PNA is usually obtained inducing (p, xn) reactions on the target nuclei by means of a proton beam of adequate energy. The large power released by the charged particle beam in biological targets (dried serum samples) requires an efficient cooling system and imposes a limitation in the beam intensity. The special irradiation chamber built to irradiate 30 samples at a time is described. An account will be given of metabolic studies on Fe, Mo, and Te in man and/or animal. Some fundamental metabolic parameters are extracted by means of compartment analysis. Data on blood serum clearance constants and relative intestinal absorption coefficients are discussed.