Bioconjugated technetium carbonyls by transmetalation reaction with zinc derivatives.

The transmetalation reaction between zinc dithiocarbamates functionalized with organic groups and the cation fac-[99mTc(H2O)3(CO)3]+ has been studied as a new strategy to bind biomolecules to this radionuclide for preparing radiopharmaceuticals with high molar activity. All complexes were obtained in high yields by heating at moderate temperatures and without subsequent purification. The chemical identity was ascertained by HPLC comparison with the homologous rhenium complexes. Stability studies in cysteine solution and serum have shown a good stability of the coordination set fac-[99mTc(CO)3(SS)(P)]. Preliminary biological studies of the radiocomplex functionalized with D-(+)-glucosamine with carcinoma cells have been performed.

New Bioconjugated Technetium and Rhenium Folates Synthesized by Transmetallation Reaction with Zinc Derivatives.

The zinc dithiocarbamates functionalized with folic acid 2Zn and 3Zn were synthesized with a simple straightforward method, using an appropriated folic acid derivative and a functionalized zinc dithiocarbamate (1Zn). Zinc complexes 2Zn and 3Zn show very low solubilities in water, making them useful for preparing Tc-99m radiopharmaceuticals with a potentially high molar activity. Thus, the transmetallation reaction in water medium between the zinc complexes 2Zn or 3Zn and the cation fac-[99mTc(H2O)3(CO)3]+, in the presence of the monodentate ligand TPPTS, leads to the formation of the 2 + 1 complexes fac-[99mTc(CO)3(SS)(P)] bioconjugated to folic acid (2Tc and 3Tc). In spite of the low solubility of 2Zn and 3Zn in water, the reaction yield is higher than 95%, and the excess zinc reagent is easily removed by centrifugation. The Tc-99m complexes were characterized by comparing their HPLC with those of the homologous rhenium complexes (2Re and 3Re) previously synthesized and characterized by standard methods. Preliminary in vivo studies with 2Tc and 3Tc indicate low specific binding to folate receptors. In summary, Tc-99m folates 2Tc and 3Tc were prepared in high yields, using a one-pot transmetallation reaction with low soluble zinc dithiocarbamates (>1 ppm), at moderate temperature, without needing a subsequent purification step.

Direct Synthesis of Rhenium and Technetium-99m Metallosurfactants by a Transmetallation Reaction of Lipophilic Groups: Potential Applications in the Radiolabeling of Liposomes.

A new zinc dithiocarbamate functionalized with palmitoyl groups is described as a useful tool for the preparation of metallosurfactants through a transmetallation reaction with the transition metals rhenium and technetium. An amphiphilic rhenium complex is synthesized by a transmetallation reaction with the zinc complex in presence of the polar phosphine sodium triphenylphosphine trisulfonate, which leads to a rhenium complex with a lipophilic dithiocarbamate and a polar phosphine ligand. The study of this rhenium complex has shown that it self-aggregates, leading to the formation of aggregates that have been analyzed by dynamic light scattering and cryotransmission electron microscopy (cryo-TEM). In addition, this amphiphilic rhenium complex is incorporated into soy phosphatidylcholine liposomes, whether liposomes are prepared by mixing phospholipid and the rhenium complex or by the incorporation of the rhenium complex into preformed liposomes. The one-pot reaction of the radiocompound [99mTc(H2O)3(CO)3]+ with the above-mentioned zinc dithiocarbamate, the phosphine sodium triphenylphosphine trisulfonate and the phospholipid soy phosphatidylcholine, leads to liposomes labeled with a Tc-99m homologous complex of the rhenium complex, in accordance with the high-performance liquid chromatography (HPLC) data.

Rhenium and technetium tricarbonyl, {M(CO)3} (+) (M = Tc, Re), binding to mammalian metallothioneins: new insights into chemical and radiopharmaceutical implications.

This paper deals with the binding of the four mammalian metallothioneins (MTs) to the organometallic metal fragment {fac-M(CO)3}(+) (M = (99)Tc, Re), which is highly promising for the preparation of second-generation radiopharmaceuticals. The study of the transmetallation reaction between zinc and rhenium in Zn7-MT1 by means of UV-vis and CD spectroscopy demonstrated the incorporation of the {fac-Re(CO)3}(+) fragment to the MTs. This reaction should be performed at 70 °C to accelerate the reaction rate, a result that is consistent with the reported reactivity of the rhenium fragment. ESI-TOF MS demonstrated the formation of mixed-metal species as Zn6,{Re(CO)3}-MT, Zn6,{Re(CO)3}2-MT, and Zn5,{Re(CO)3}3-MT, as well as the different reactivity of the four MT isoforms. Hence, Zn-MT3 showed the highest reactivity, in agreement with its high Cu-thionein character, whereas Zn-MT2 exhibited the lowest reactivity, in line with its high Zn-thionein character. The reactivity of the Zn-loaded forms of MT1 and MT4 is intermediate between those of MT3 and MT2. The study of the binding of the {fac-(99)Tc(CO)3}(+) fragment to MTs showed a significant and very interesting different reactivity in relation to rhenium. The transmetallation reaction is much more effective with technetium than with rhenium and significant amounts of mixed Zn x ,{(99)Tc(CO)3} y -MT species were formed with the four MT isoforms whereas only MT3 rendered similar amounts of rhenium derivatives. The results obtained in this study support the possible use of technetium for labelling mammalian metallothioneins and also for possible radiopharmaceutical applications.

New rhenium complexes with ciprofloxacin as useful models for understanding the properties of [99mTc]-ciprofloxacin radiopharmaceutical.

Rhenium complexes with the antibiotic ciprofloxacin have been prepared to be studied as models of technetium radiopharmaceuticals. With this aim, the new rhenium complexes 1 {[ReO(Cpf)2]Cl}, 2 {[ReO(CpfH)2]Cl3} and 3 {fac-[Re(CO)3(H2O)(Cpf)]} with ciprofloxacin (CpfH=ciprofloxacin; Cpf=conjugated base of ciprofloxacin) have been synthesised and characterised by elemental analyses, IR, NMR ((1)H, (19)F and (13)C CP-MAS) spectroscopy, as well as MS measurements. All spectroscopic data are consistent with the coordination of ciprofloxacin in all these complexes through the carbonyl and the carboxylate oxygen atoms with the formation of a six member chelate ring. The study of a Tc-ciprofloxacin solution by ESI-MS reveals the presence of [TcO(Cpf)2](+) cations, which agrees with the hypothesis that complexes 1 and 2 can be seen as model rhenium complexes of this radiopharmaceutical. Antimicrobial and DNA gyrase inhibition studies performed with complexes 2 and 3 have shown a very similar behaviour between complex 2 and the free antibiotic, whereas complex 3 exhibit a lower antimicrobial activity. Based on a joint analysis of the data reported in the literature and the chemical and biological results obtained in this study, a tentative proposal to explain some aspects of the behaviour of Tc-ciprofloxacin radiopharmaceutical has been made.

New surfactant phosphine ligands and platinum(II) metallosurfactants. Influence of metal coordination on the critical micelle concentration and aggregation properties.

We have prepared the first platinum(II) metallosurfactants from a new family of linear surfactant phosphines Ph(2)P(CH(2))(n)SO(3)Na {1 (n = 2), 2 (n = 6), and 3 (n = 10)}, which were synthesized by reaction between the halosulfonates X(CH(2))(n)SO(3)Na and sodium diphenylphosphide. The metallosurfactants cis-[PtCl(2)L(2)] (L = 1-3) were obtained after reaction between the phosphines and PtCl(2) in dimethylsulfoxide. All compounds were fully characterized by the usual methods {NMR ((1)H, (13)C, (31)P, (195)Pt), IR, MS-ESI and HRMS}. By exploring the surfactant properties of phosphines 1-3 and their respective platinum metallosurfactants cis-[PtCl(2)L(2)] (L = 1-3) through surface tension measurements, dynamic light scattering spectroscopy, and cryo-TEM microscopy, we were able to analyze the influence of the metal coordination on the critical micelle concentration (cmc) and the aggregation properties. The cmc values of platinum metallosurfactants were considerably lower than those obtained for the free phosphines 1-3. This behavior could be understood by an analogy between the structure of cis-[PtCl(2)L(2)] complexes and bolaform surfactants. The calculated values of area per molecule also showed different tendencies between 1-3 and cis-[PtCl(2)L(2)] complexes, which could be explained on the basis of the possible conformations of these compounds in the air-water interface. The study of aggregates by dynamic light scattering spectroscopy and cryo-TEM microscopy showed the formation of spherical disperse medium size vesicles in all cases. However, substantial differences were observed between the three free phosphines (the population of micellar aggregates increased with long chain length) and also between phosphines and their respective metallosurfactants.

Formation of vesicles with an organometallic amphiphile bilayer by supramolecular arrangement of metal carbonyl metallosurfactants.

Metallo-vesicles are formed in water medium as a result of the supramolecular arrangement of molybdenum carbonyl metallosurfactants. These new kind of surfactants contain a hydrophobic metal carbonyl fragment and are easily prepared from surfactant phosphine ligands.

Usefulness of 99mTc-ciprofloxacin scintigraphy in the diagnosis of prosthetic joint infections.

OBJECTIVE: To evaluate the usefulness of 99Tc-ciprofloxacin scintigraphy (CFS) in patients with hip or knee arthroplasty and suspected infection. METHODS: Forty patients (26 women, 14 men) with a mean age of 66±10 years and local pain in the hip (21), knee (16), or shoulder (three) prosthesis were recruited. CFS was performed at 1, 4, and 24 h after intravenous injection of 370 MBq. Anterior and posterior views centered on the affected joint were performed in all patients. A routine bone scan, 99Tc-hexamethylpropyleneamine oxime leukocyte scan, and 99Tc-colloid scan [leukocyte scintigraphy-bone marrow scintigraphy (LS-MS)] were performed. Final diagnosis of infection was confirmed by positive microbiological analysis or macroscopic evidence of purulent material. RESULTS: Diagnosis of arthroplasty infection was established in 16 out 40 cases: coagulase-negative staphylococci (nine), Staphylococcus aureus (three), Enterococcus (one), and macroscopic infection in the remaining three cases. CFS imaging showed the 24-h image to be the best acquisition time-point. The sensitivity, specificity, negative predictive value, and positive predictive value for LS-MS were 75, 92, 86, and 85%, whereas for CFS at 24 h these figures were 88, 71, 67, and 89%. The sensitivity and specificity for LS-MS and for CFS at 24 h for hip were (74, 90, and 88, 85%) and for knee (83, 90 and 100, 50%). CONCLUSION: CFS can be useful in the diagnosis of arthroplasty infection of the hip as a substitute for LS-MS. It is recommended that CFS images be obtained 24 h after injection. The lack of specificity of CFS makes this technique inadequate for knee prostheses in this series.