Possibilites et limites de l'analyse par activation neutronique multielementaire d'echantillons biologiques avec ou sans separation de la matrice activable

The possibilities and limits of the multi-elemental determinations in biological samples by neutron activation analysis with and without chemical separation are discussed.      

Enantioselective syntheses of no-carrier-added (n.c.a.) (s)-4-chloro-2-[f] fluorophenylalanine and (s)-(α-methyl) -4-chloro-2-[f]fluorophenylalanine

(S)-4-Chloro-2-fluorophenylalanine and (S)-(α-methy)-4-chloro-2-fluorophenylalanine were synthesized and labeled with no carrier added (n.c.a.) fluorine-18 through a radiochemical synthesis relying on the highly enantioselective reaction between 4-chloro-2-[¹⁸F]fluorobenzyl iodide and the lithium enolate of (2S)-1-(tert-butyloxycarbonyl)-2-(tert-butyl)-3-methyl-1,3-imidazolidine-4-one for (S)-4-chloro-2-[¹⁸F]fluorophenylalanine and (2S,5S)-1-(tert-butyloxycarbonyl)-2-(tert-butyl)-3,5-dimethyl-1,3-imidazolidine-4-one for (S)-(α-methyl) -4-chloro-2-[¹⁸F] fluorophenylalanine. Quantities of about 20–25 mCi were obtained at the end of sy nthesi s, ready for injection after hydrolysis and high performance liquid chromatography (HPLC) purification, with a radiochemical yield of 17%–20% corrected to the end of bombardment after a total synthesis time of 90–105 min from [¹⁸F] fluoride. The enantiomeric excesses were shown to be 97% or more for both molecules without chiral separation and the radiochemical and chemical purities were 98% or better.     

The employment of relativistic adapted Gaussian basis sets in Douglas–Kroll–Hess scalar calculations with diatomic molecules

The prolapse-free relativistic adapted Gaussian basis sets (RAGBSs), developed by our research group on the basis of the four-component approach, are used for the first time in Douglas–Kroll–Hess 2nd order scalar relativistic calculations (DKH2) of simple diatomic molecules containing Hydrogen and the halogens from Fluorine up to Iodine: HX and X₂, where X = F, Cl, Br, and I. To this end, the RAGBSs were contracted with the general contraction scheme to triple-, quadruple-, and quintuple-zeta sets. Polarization functions were also added to the basis sets by optimization with the configuration interaction method including single and double excitations into the DKH2 environment, DKH2-CISD. The molecular properties were then calculated with the coupled cluster electronic correlation treatment and the DKH2 scalar relativistic method, DKH2-CCSD(T), and indicated that our RAGBSs should be contracted as quadruple-zeta basis sets. The results achieved with the DKH2-CCSD(T) calculations and the selected quadruple-zeta RAGBSs are able to reproduce the experimental data of equilibrium distances, dissociation energies, and harmonic vibrational frequencies with root-mean-square (rms) errors of 0.015 Å, 3.6 kcal mol⁻¹, and 21.7 cm⁻¹, respectively.     

Multi-element analysis of biological samples after intense neutron irradiation an fast chemical separation

For the simultaneous determination of many elements in small biological samples, a multi-element analysis has been developed using neutron activation. After a 24-hr irradiation in a neutron flux of 2.5·10¹⁴ n·cm⁻²·sec⁻¹ and after immediate chemical separation without cooling, it was possible to analyse 24 elements in bovine liver (NBS-SRM 1577). The separation apparatus, set up in a shielded cell can work four samples simultaneously, and its operation is fast enough to allow the detection of radioisotopes with a half-life of about 2 hrs (¹⁶⁵Dy,^57mSr,⁵⁶Mn). Amounts lower than 10⁻³ μg of Dy, Eu, Pr, Sm and Yb were determined.     

In vivo measurement of the Ca/P ratio by local activation with isotopic neutron sources

In connection with the study and the treatment of generalised demineralising bone diseases, the amount of phosphorus and calcium has been determined in the hand by “in vivo” neutron activation analysis using²⁵²Cf and²³⁸Pu−Be isotopic neutron sources. The statistical accuracy of the induced radioactivity measurement carried out on the hand of a normal subject is about 2% for P and Ca, while the standard deviation over a series of 10 analyses performed on a same phantom remains within 3% for both P and Ca. The results are normalized and expressed in grams of P or Ca per cm³ of bone. The values observed on a group of 55 normal subjects and on some osteoporotic patients are given.     

11C-labelled etorphine for “in vivo” studies of opiate receptors in brain

In order to study “in vivo” opiate receptors, a method for¹¹C labelling of etorphine is described. 80 mCi (max. 120 mCi) of injectable labelled product radiochemically and chemically pure, are obtained in 25 minutes with a specific activity of 800 mCi/μmol.     

In vitro preparation of68Ga-labelled transferrin

Systematic investigations into the practical problems of labelling transferrin with⁶⁸Gain vitro are presented. A chemical purification of the⁶⁸Ga generator eluate is described and the working conditions whereby several millicuries of⁶⁸Ga may be bound quantitatively onto a few milligrams of transferin are defined.     

11C-methiodide quinuclidinyl benzilate a muscarinic antagonist for in vivo studies of myocardial muscarinic receptors

A method for labeling MQNB (Methiodide quinuclidinyl benzilate) with carbon-11 using¹¹C-methyl iodide is reported. Injectable labeled product (100 mCi; max. 200 mCi) radiochemically and chemically pure is obtained in a 30 minute synthesis time with a specific activity of 1 Ci/μmol, (max. 2.3 Ci/μmol).     

Effects of Citrus aurantium (bitter orange) fruit extracts and p-synephrine on metabolic fluxes in the rat liver

The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as weight-loss products and as appetite supressants. An important fruit component is p-synephrine, which is structurally similar to the adrenergic agents. Weight-loss and adrenergic actions are always related to metabolic changes and this work was designed to investigate a possible action of the C. aurantium extract on liver metabolism. The isolated perfused rat liver was used to measure catabolic and anabolic pathways, including oxygen uptake and perfusion pressure. The C. aurantium extract and p-synephrine increased glycogenolysis, glycolysis, oxygen uptake and perfusion pressure. These changes were partly sensitive to α- and β-adrenergic antagonists. p-Synephrine (200 μM) produced an increase in glucose output that was only 15% smaller than the increment caused by the extract containing 196 μM p-synephrine. At low concentrations the C. aurantium extract tended to increase gluconeogenesis, but at high concentrations it was inhibitory, opposite to what happened with p-synephrine. The action of the C. aurantium extract on liver metabolism is similar to the well known actions of adrenergic agents and can be partly attributed to its content in p-synephrine. Many of these actions are catabolic and compatible with the weight-loss effects usually attributed to C. aurantium.     

Possibilites et limites de l’analyse d’echantillons biologiques par activation neutronique derriere ecran de cadmium

The analytical possibilities offered by long-term irradiation of biological samples in a fission neutron flux filtered by a cadmium screen are examined and the preparation of samples for irradiation is described. This specific activation technique is applied to the determination of molybdenum and nickel in the following three reference substances: human serum, NBS bovine liver and BOWEN’s kale.