A. E. Miroslavov

Evaluation of 99mTc(CO)5I as a potential lung perfusion agent

INTRODUCTION The use of (99m)Tc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. However, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, Variant Creutzfeldt Jakob Disease. Preliminary work has indicated that Tc(CO)(5)I is primarily taken up in the lungs following intravenous administration. The aim of this study was to evaluate the biodistribution and pharmacokinetics of (99m)Tc(CO)(5)I and its potential as a lung perfusion agent. METHODS (99m)Tc(CO)(5)I was synthesized by carbonylation of (99m)TcO(4-) at 160 atm of CO at 170 degrees C in the presence of HI for 40 min. Radiochemical purity was determined by HPLC using (99)Tc(CO)(5)I as a reference. (99m)Tc(CO)(5)I was administered by ear-vein injection to three chinchilla rabbits, and dynamic images were acquired using a gamma camera (Siemens E-cam) over 20 min. Imaging studies were also performed with (99m)Tc-labeled macroaggregated albumin ((99m)Tc-MAA) and (99m)TcO(4-) for comparison. (99m)Tc(CO)(5)I was administered intravenously to Sprague-Dawley rats, and tissue distribution studies were obtained at 15 min and 1 h postinjection. Comparative studies were performed using (99m)Tc-MAA. RESULTS Radiochemical purity, assessed by HPLC, was 98%. The retention time was similar to that of (99)Tc(CO)(5)I. The dynamic images showed that 70% of (99m)Tc(CO)(5)I appeared promptly in the lungs and remained constant for at least 20 min. In contrast, (99m)TcO(4-) rapidly washed out of the lungs after administration. As expected (99m)Tc-MAA showed 90% lung accumulation. The percentage of injected dose per gram of organ +/-S.D. at 1 h for (99m)Tc(CO)(5)I was as follows: blood, 0.22+/-0.02; lung, 12.8+/-2.87; liver, 0.8+/-0.15; heart, 0.15+/-0.01; kidney, 0.47+/-0.08. The percentage of injected dose per organ +/-S.D. at 1 h was as follows: lung, 22.47+/-2.31; liver, 10.53+/-1.8; heart, 0.18+/-0.01; kidney, 1.2+/-0.17. Tissue distribution studies with (99m)Tc-MAA showed 100% lung uptake. CONCLUSION (99m)Tc(CO)(5)I was synthesized with a high radiochemical purity and showed a high accumulation in the lungs. Further work on the mechanism and optimization of lung uptake of (99m)Tc-pentacarbonyl complexes is warranted.

Technetium(I) carbonyl dithiocarbamates and xanthates.

Technetium(I) tetracarbonyl complexes with diethyldithiocarbamate and methylxanthate ligands [TcL(CO)(4)] (L = S(2)CNEt(2) and S(2)COMe) were prepared. Conditions required for the formation of these complexes were found. The crystal and molecular structure of the xanthate complex was determined by single-crystal X-ray diffraction. [Tc(S(2)CNEt(2))(CO)(4)] undergoes decarbonylation both in solution and in the course of vacuum sublimation with the formation of a dimer [Tc(S(2)CNEt(2))(CO)(3)](2) whose structure was determined by single-crystal X-ray diffraction. In donor solvents, [Tc(S(2)CNEt(2))(CO)(4)] and [Tc(S(2)COMe)(CO)(4)] undergo decarbonylation with the formation of tricarbonyl solvates [TcL(CO)(3)(Sol)]. The crystal structure of the pyridine solvate [Tc(S(2)CNEt(2))(CO)(3)(py)], chosen as an example, was determined by single-crystal X-ray diffraction. The possibility of using bidentate S-donor acidic ligands for tethering the tetracarbonyltechnetium fragment to biomolecules was examined.

Technetium and Rhenium Pentacarbonyl Complexes with C2 and C11 ω-Isocyanocarboxylic Acid Esters

Technetium(I) and rhenium(I) pentacarbonyl complexes with ethyl 2-isocyanoacetate and methyl 11-isocyanoundecanoate, [M(CO)5(CNCH2COOEt)]ClO4 (M = Tc (1) and Re (2)) and [M(CO)5(CN(CH2)10COOMe)]ClO4 (M = Tc (3) and Re (4)), were prepared and characterized by IR, (1)H NMR, and (13)C{(1)H} NMR spectroscopy. The crystal structures of 1 and 2 were determined using single-crystal X-ray diffraction. The kinetics of thermal decarbonylation of technetium complexes 1 and 3 in ethylene glycol was studied by IR spectroscopy. The rate constants and activation parameters of this reaction were determined and compared with those for [Tc(CO)6](+). It was found that rhenium complexes 2 and 4 were stable with respect to thermal decarbonylation. Histidine challenge reaction of complexes 1 and 2 in phosphate buffer was examined by IR spectroscopy. In the presence of histidine, the rhenium pentacarbonyl isocyanide complex partially decomposes to form an unidentified yellow precipitate. Technetium analogue 1 is more stable under these conditions.

Complexation of Tricarbonyltechnetium(I) Ion with Halide and Thiocyanate Ions in Aqueous Solution: 99Tc NMR Study

Complexation of the Tc(CO)3(H2O)3+ ion with halide (F-, Cl-, Br-, I-) and thiocyanate ions in aqueous solutions was studied by 99Tc NMR spectroscopy. The stability constants of the mono-, di-, and tri- substituted complexes were calculated. The stability of halide (Cl-, Br-, I-) complexes grows as the ionic radius of the halogen increases and its electronegativity decreases. For halide complexes of similar composi- tion, the 99Tc chemical shift correlates with the stability of the complexes. The fluoride ion, most probably, does not coordinate with the Tc(CO)3+ ion, in contrast to its close analog, hydroxide ion. Among the ligands studied, the pseudohalide anion NCS- forms the most stable complexes with the Tc(CO)3+ ion.

Reactivity of Tc(I) tetracarbonyl complexes

Technetium tetracarbonyl complexes [TcBr(CO)4]2 and [TcXan(CO)4] (Xan is methylxanthate), being fairly stable in an inert solvent, undergo rapid decarbonylation in a donor solvent (acetonitrile). The kinetic characteristics of the reaction were determined. The experimental data and results of quantum-chemical calculations allow a conclusion that the reaction, as in the case of pentacarbonyl halides, occurs via dissociative pathway with a lower energy barrier as compared to pentacarbonyl halides. The results obtained were interpreted assuming the formation of unstable complexes of intermediate five-coordinate technetium species with an “inert” solvent molecule and the effect of this phenomenon on the relative stability of the technetium penta- and tetracarbonyl complexes. The technetium complex [TcXan(CO)4] is considerably less stable than its rhenium analog.

Preparation of unsupported granulated triuranium octoxide and its use as catalyst of conversion of ammonium nitrate to nitrogen in an NH 4 NO 3 –H 2 O vapor–gas mixture

Formulation of the forming paste for preparing unsupported granulated triuranium octoxide U3O8 was developed. The mixture contains U3O8 and (NH4)2U2O7 in a weight ratio from 1: 1 to 1: 1.5, and also water in an amount of 25–40 wt % relative to the sum of the dry components. Calcination of crude granules at 800–1100°С results in formation of strong ceramic granules with 57–45% open porosity, consisting of U3O8. Granulated U3O8 efficiently catalyzes the conversion of ammonium nitrate to nitrogen in an NH4NO3–H2O vapor–gas mixture with the addition of ammonium carbonate. The absence of support makes the catalyst composition more definite and simplifies its regeneration.

Specific features of the cis labilization effect in the series of pentacarbonyltechnetium halides

Causes of abnormal (from the viewpoint of traditional views on the cis labilization effect) enhancement of the tendency of pentacarbonyltechnetium halides to decarbonylation in the series I–Br–Cl–F are discussed. Two possible causes are considered: “nonclassical” halogen···cis-C interaction and electrostatic interactions of the halide ligand with the Tc atom in the initial complex and pentacoordinate transition state. Relative stabilization of the transition state due to electrostatic interactions is concluded to be the most probable cause of the observed trend.