M. Vidal

Nitroimidazoles and hypoxia imaging: synthesis of three technetium-99m complexes bearing a nitroimidazole group: biological results

Several Tc-99m complexes were synthesized, substituted with a nitroimidazole group, in order to visualize hypoxic tissues. The complexes were tested on rats (isolated hearts) and showed no significant uptake under hypoxic conditions.

[123I]-6-deoxy-6-iodo-d-glucose (6DIG): A potential tracer of glucose transport

A glucose analogue labelled with iodine-123 in position 6 has been synthesized: [123I]-6-deoxy-6-iodo-D-glucose (6DIG). The aim of this study was to examine its biological behaviour in order to assess whether it could be used to evaluate glucose transport with SPECT. To establish whether 6DIG enters the cells using the glucose transporter, four biological models have been used: human erythrocytes in suspension, neonatal rat cardiomyocytes in culture, isolated perfused rat hearts, and biodistribution in mice. 6DIG competed with D-glucose to enter the cells and its entry was increased by insulin and inhibited in the presence of cytochalasin B. The biological behaviour of 6DIG was similar to that of 3-O-methyl-D-glucose. 6DIG is a tracer of glucose transport which is very promising for clinical studies.

Biological studies of analogues of glucose iodinated in positions 1, 2, or 3

Analogues of glucose labeled with 123 iodine in positions 1, 2 or 3 have been synthesized. The aim of this study was to examine their biological behavior in four experimental models in order to assess whether they could be used to evaluate the uptake of glucose with single photon emission computed tomography (SPECT). The results obtained have shown that none of these molecules enters the cell using the glucose transporter. Therefore, they cannot be used as tracers of glucose uptake.

Synthesis of 3-O-(2-iodoethyl)-d-glucose, a stable iodo derivative of d-glucose for medical imaging

2-Deoxy-2-fluoro-D-glucose is an almost ideal tracer for D-glucose transport and metabolic uptake, with the limitation however that the cyclotron-produced positron-emitter “F isotope has a short half-life and, consequently, the use of 18F-labelled glucose derivatives for medical imaging is necessarily heavily restricted. Consequently, there has been a general search for D-glucose analogues in which iodine isotope gamma-emitters would be the detector group. Unfortunately, the corresponding iodo analogue of 2-deoxy-2-fluoro-D-glucose, namely 2-deoxy-2iodo-D-glucose, is notably unstablele3. Other simple iodo derivatives of D-glucose, of variable stability, have been prepared2.4-7. Our current approach to suitable iodinated D-glucose tracers aims at the compounds in which the supplementary iodine-bearing group, while being stable enough, would be as small as possible so as to minimize unfavorable interactions with the D-glucose transporter8P9. The known stability10-‘3 of P-iodoethers prompted us to incorporate this unit into a D-glucose skeleton. This approach has already resulted in the preparation of 2-iodoethyl P-D-glucopyranoside14, a close analogue of propyl P-D-glucopyranoside, but which does not compete with D-glucose for entry into the ce1115. Since 3-O-p ro py I-D-glucose is known to compete with the natural substrate for its passive transport 16, the preparation of the corresponding 2-iodoether 1 became the target of choice. For the synthesis of 3-0-(2-iodoethylj-D-glucose Cl), literature methods for the direct introduction17-23 of a P-iodoether cannot be applied. Among other approaches tried, it is noteworthy that reaction of the silyl or sulfonyl derivatives of 2-iodoethanol gave only products resulting from an attack of the oxyanion derived

Synthese de nouveaux oxydes de tetraphosphines macrocycliques

Abstract The direct cycloadditions of two dioxophosphidure dianons with two molecules of an unsaturated dihalide produce unsaturated macrocyclic phosphine tetraoxides that are alkylated on phosphorus. Their reduction by molecular hydrogen is highly selective: the saturated homologues are obtained in excellent yield.

Biological evaluation of two anomeric glucose analogues iodinated in position

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.

Synthesis and characterization of new diisocyanide rhenium complexes. Comparison with the homoleptic 99mTc complex

Abstract The new diisocyanide ligand L possessing a polyether backbone was synthesized and its complexing ability towards metal such as 99mTc, Cu and Re was evaluated. Using the γ-emitting 99mTc isotope (at the non-carrier added level), L led to the formation of a cationic species whose biodistribution in Swiss mice revealed a moderate but lasting heart uptake. No redox properties of the ligand were observed by complexation since reaction with a CuII salt led to the formation of a CuII complex, characterized by EPR, IR and elemental analysis. Rhenium complexation gave two new chelates [ReIIICl3PPh3L] and [ReI3]BPh4, identified by IR NMR, elemental analysis and conductimetric studies. The usefulness of rhenium chemistry to approach 99mTc properties is discussed.

Complexation of alkali metal and tetramethylammonium ions with polyacids. pH-Metry consequences

Mass Spectrometry (MS) enables the study of alkali metal and tetramethylammonium (TMA) complexes which are formed during potentiometric titrations. Their formation and their evolution as a function of pH are confirmed by means of 23Na NMR spectroscopy. This is a common phenomenon which calls the principle of pH-metric titration of polyacids into question.

Synthese de polyamines macrocycliques. Complexation du coeur [99mTcO+2] et biodistribution des complexes formes

Resume La synthese de tetramines cycliques, de tetramines cycliques mono-et tetra-N-alkylees est developpee ainsi que la complexation due technetium par ces ligands a partir de 99m TcO − 4 . Plusieurs reducteurs du pertechnetate sont etudies ainsi que le rendement de complexation, la charge et la lipophilie des complexes. Leur etude biologique chez la souris (biodistribution) et chez le chien (scintigraphie) a permis de mettre en evidence une excellente captation hepatobiliaire du trans - 99m TcO 2 (1-dodecyl-1,4,8,11-tetraazacylotetradecane).

Nouvelles réactions d'ouverture basique an série halogénocycloproganique fonctionnalisée

Abstract Nonohalocyclopropyl alcohols, obtained by halocarbenoid cycloaddition can produce unusual α-allenyl or α-dienyl alcohols on reactions with activated lithium diethylamide.