2 + 1 Tricarbonyl Complexes of Technetium(I) with a Combination of N,N-Bidentate Ligands and Ethyl Isocyanoacetate: How Strong Is the Interfering Effect of Chloride Ions on Their Formation?

Technetium(I) 2 + 1 tricarbonyl complexes with a combination of N,N-bidentate ligands (2,2'-bipyridine, bipy; 1,10-phenanthroline, phen) and ethyl isocyanoacetate were prepared and characterized by NMR, IR, UV/visible, and luminescence spectroscopies and by high-performance liquid chromatography (HPLC). The crystal structures of [99Tc(CO)3(bipy)(CNCH2COOEt)](ClO4) (in the form of a solvate with 0.5CH2Cl2) and [99Tc(CO)3(phen)(CNCH2COOEt)](ClO4) (in the form of an adduct with an outer-sphere phen molecule) were determined by single-crystal X-ray diffraction. To evaluate the interfering effect of chloride ions on the formation of the 2 + 1 complexes, the kinetics of the replacement of labile monodentate ligand X in the complexes [MX(CO)3(N∧N)] (M = Re, 99Tc; N∧N = bipy, phen; X = Cl-, ClO4-) by CNCH2COOEt in ethanol were compared. The 99Tc bipy complexes with X = ClO4- (according to the IR data, perchlorate anion in ethanol is displaced from the coordination sphere by the solvent molecule) and X = Cl- are characterized by close ligand replacement rates. In the case of the 99Tc complexes with phen and Re complexes with both phen and bipy, the chloride complexes are appreciably less reactive than the chloride-free complexes. The technetium complexes are considerably more reactive in ligand replacement than their rhenium analogues. In the chloride-containing medium (saline), the complex [99mTc(CO)3(bipy)(CNCH2COOEt)]+ can be prepared under the conditions acceptable for nuclear medical applications, although higher isonitrile concentrations are required as compared to the chloride-free system.

Hydrolysis of Hexacarbonyltechnetium(I) Cation: Formation and Structure of Technetium Carbonyl Hydride 99Tc3H(CO)14.

Reaction of [99Tc(CO)6]ClO4 with alkali in aqueous solutions yields yellow 99Tc3H(CO)14 as the major product. On the other hand, [99TcH(CO)5] becomes the major product when the reaction with alkali is combined with the extraction into hexane. The molecular structure of 99Tc3H(CO)14, determined by SCXRD, is composed of the 99Tc2(CO)9 fragment bound to the 99Tc(CO)5 fragment via the hydrogen bridge and weak metal-metal bond. This compound crystallizes in the monoclinic system, space group P21/n, a = 9.6954(2) Å, b = 15.0985(3) Å, c = 14.5090(3) Å, and ß = 104.925(2)°. 99Tc3H(CO)14 was additionally characterized by IR spectroscopy. The mechanism of hydrolysis of [99Tc(CO)6]ClO4 was suggested.

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.

Synthesis, characterization and pre-clinical evaluation of (99m) Tc-tricarbonyl complexes as potential myocardial perfusion imaging agents.

Myocardial perfusion imaging is an established Nuclear Medicine investigation. Current myocardial perfusion imaging agents sestamibi and tetrofosmin have number of drawbacks; low heart uptake coupled with uptake into the surrounding tissues leads to a poorer image quality. There is a need for continued research into designing and evaluating potentially superior myocardial imaging agents. Tri-carbonyl-technetium and rhenium complexes were prepared by combination with mono-dentate and bi-dentate ligands. Complexes were characterized by HPLC, MAS, nuclear magnetic resonance, infrared, single-crystal X-ray diffraction and partition coefficient determinations. (99m) Tc(CO)3 complexes were administered intravenously to Sprague Dawley rats, and tissue distribution studies were carried out at 15 min and 1 h p.i. Radiochemical purity was assessed as >90%. 1-10-phenanthroline, 2,2'-bipyridine and imidazole complexes gave the highest heart uptake. The percentage injected dose per gram (n = 3) at 1 h for 1-10-phenanthroline/imidazole was blood 0.21 ± 0.01, heart 1.12 ± 0.11, kidney 3.61 ± 1.13, liver 0.62 ± 0.06, lung 0.28 ± 0.12, spleen 0.24 ± 0.05, small intestine contents 1.87 ± 0.92; and for 2,2'-bipyridine /imidazole was blood 0.23 ± 0.02, heart 1.07 ± 0.18, kidney 3.31 ± 1.28, liver 0.56 ± 0.09, lung 0.14 ± 0.02, spleen 0.2 ± 0.1, small intestine content 1.05 ± 0.48. Further investigation to evaluate more complexes based on 1,10-phenanthroline, 2,2'-bipyridine and imidazole derivatives could potentially lead to agents with an increased heart uptake and faster clearance from the liver and gastrointestinal tract.

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.