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Research paper thumbnail of A class of asymmetrical nitrido 99m Tc heterocomplexes as heart imaging agents with improved biological properties

Asymmetrical heterocomplexes containing a terminal technetium±nitrogen multiple bond coordinated ... more Asymmetrical heterocomplexes containing a terminal technetium±nitrogen multiple bond coordinated to one diphosphine ligand (PNP) and one dithiocarbamate ligand (DBODC), were obtained through a simple two-step procedure under controlled conditions. The resulting complexes [ 99m Tc(N)(PNP)(DBODC)] + are monocationic, and possess a distorted square±pyramidal geometry where the Tc:N multiple bond occupies an apical position and the diphosphine and dithiocarbamate ligands span the residual four coordination positions on the basal plane through the two phosphorus atoms and the two sulfur atoms, respectively. Biodistribution data in rats demonstrated that these complexes were rapidly extracted by the myocardium, and retained in this region for a prolonged time. After a few minutes post-injection, lung uptake became negligible, and liver washout was extremely rapid and quantitative. Analysis of heart/liver uptake ratios for these complexes revealed that their values increased exponentially in time, and after 60 min post-injection liver activity was almost completely eliminated into the intestine. Comparison with heart/liver ratios determined for 99m Tc sestamibi and 99m Tc tetrfosmin showed that values for these latter compounds were approximately 10 times lower than those measured for [ 99m Tc(N)(PNP)(DBODC)] + complexes at 60 min post-injection. In conclusion, the monocationic tracers [ 99m Tc(N)(PNP)(DBODC)] + exhibit high myocardial uptake in rats and dramatically high heart/lung and heart/liver ratios, suggesting that this novel class of perfusion agents could be conveniently employed to obtain heart images with superior imaging quality. (# 2002 Lippincott Williams & Wilkins)

Research paper thumbnail of Yap-(s)pet small animal scanner: quantitative results

IEEE Transactions on Nuclear Science, 2003

The University of Ferrara YAP-(S)PET scanner is currently being employed in small animal SPECT st... more The University of Ferrara YAP-(S)PET scanner is currently being employed in small animal SPECT studies, with 99 m Tc labeled radiotracers, with the goal of obtaining quantitative activity measurements from region of interest (ROI) analysis of reconstructed images of rats. The measurements will be compared directly with traditional ex vivo measurement of activity with gamma counters. To achieve this goal, the scanner was calibrated relative to a standard Isodose dose calibrator which was calibrated with various certified activity sources. The calibration factor K was defined as the ratio of the activity measured with the Isodose (MBq) and the image count rate (cps). We find K = 0 1346 0 0008 MBq cps, with good linearity over a wide range of activities (9-88 MBq). With the calibrated scanner we compared results of activity measurements from images of whole-rat heart acquisitions versus excised hearts. We found good agreement between the two measurements.

Research paper thumbnail of Rhenium(V) and Technetium(V) Nitrido Complexes with Mixed Tridentate π-Donor and Monodentate π-Acceptor Ligands

Inorganic Chemistry, 2012

Mixed-ligand [M(N)(SNS)(PPh(3))] complexes (M = Tc, Re) (1, 2) were prepared by reaction of the p... more Mixed-ligand [M(N)(SNS)(PPh(3))] complexes (M = Tc, Re) (1, 2) were prepared by reaction of the precursor [M(N)Cl(2)(PPh(3))(2)] with ligand 2,2'-dimercaptodiethylamine [H(2)SNS = NH(CH(2)CH(2)SH)(2)] in refluxing dichloromethane/ethanol mixtures. In these compounds, 2,2'-dimercaptodiethylamine acts as a dianionic tridentate chelating ligand bound to the [M≡N](2+) group through the two π-donor deprotonated sulfur atoms and the protonated amine nitrogen atom. Triphenylphosphine completes the coordination sphere, acting as a monodentate ligand. [M(N)(NS(2))(PPh(3))] complexes can assume two different isomeric forms depending on the syn and anti orientations of the hydrogen atom bound to the central nitrogen atom of the SNS ligand with respect to the M≡N moiety. X-ray crystallography of the syn isomer of complex 2 demonstrated that it has a distorted trigonal bipyramidal geometry with the nitrido group and the two sulfur atoms defining the equatorial plane, the phosphorus atom of the monophosphine and the protonated amine nitrogen of the tridentate ligand spanning the two reciprocal trans positions along the axis perpendicular to the trigonal plane. Synthesis of the analogous Tc derivatives with tris(2-cyanoethyl)phosphine, [Tc(N)(SNS)(PCN)] [(PCN = P(CH(2)CH(2)CN)(3)], required the preliminary preparation of the new precursor [Tc(N)(PCN)(2)Cl(2)](2) (3), which was prepared by reacting [n-NBu(4)][Tc(N)Cl(4)] with a high excess of PCN. The crystal structure of compound 3 consists of a noncrystallographic centrosymmetric dimer of Tc(V) nitrido complexes having an octahedral geometry. In this arrangement, the apical positions are occupied by two tris(2-cyanoethyl)phosphine groups and the equatorial positions by the nitrido group whereas the two Cl(-) anions and one cyano ligand belong to the other octahedral component of the dimer. By reacting the new precursor [Tc(N)(PCN)(2)Cl(2)](2) with the ligand H(2)SNS the complex [Tc(N)(SNS)(PCN)] (5) was finally obtained in acetonitrile solution. The new Tc(III) complex trans-[Tc(PCN)(2)Cl(4)][n-NBu(4)] (4) was also isolated from the reaction solution used for preparing complex 3 as side product and characterized by X-ray diffraction. The crystal structure of 4 consists of independent trans-[TcCl(4)(PCN)(2)](-) anions situated on crystallographic centers of symmetry and tetrabutylammonium cations in general positions.

Research paper thumbnail of Preparation and first biological evaluation of novel Re-188/Tc-99m peptide conjugates with substance-P

Applied Radiation and Isotopes, 2014

New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically ... more New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N](2+) (M=(99m)Tc, (188)Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands. The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N](2+) core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas the monodentate ligand was a tertiary phosphine. The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re≡N](2+) core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small-animal YAP(S)PET tomograph. New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high-yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re-188 radiopharmaceuticals exhibit identical biological properties.

Research paper thumbnail of A class of asymmetrical nitrido 99m Tc heterocomplexes as heart imaging agents with improved biological properties

Asymmetrical heterocomplexes containing a terminal technetium±nitrogen multiple bond coordinated ... more Asymmetrical heterocomplexes containing a terminal technetium±nitrogen multiple bond coordinated to one diphosphine ligand (PNP) and one dithiocarbamate ligand (DBODC), were obtained through a simple two-step procedure under controlled conditions. The resulting complexes [ 99m Tc(N)(PNP)(DBODC)] + are monocationic, and possess a distorted square±pyramidal geometry where the Tc:N multiple bond occupies an apical position and the diphosphine and dithiocarbamate ligands span the residual four coordination positions on the basal plane through the two phosphorus atoms and the two sulfur atoms, respectively. Biodistribution data in rats demonstrated that these complexes were rapidly extracted by the myocardium, and retained in this region for a prolonged time. After a few minutes post-injection, lung uptake became negligible, and liver washout was extremely rapid and quantitative. Analysis of heart/liver uptake ratios for these complexes revealed that their values increased exponentially in time, and after 60 min post-injection liver activity was almost completely eliminated into the intestine. Comparison with heart/liver ratios determined for 99m Tc sestamibi and 99m Tc tetrfosmin showed that values for these latter compounds were approximately 10 times lower than those measured for [ 99m Tc(N)(PNP)(DBODC)] + complexes at 60 min post-injection. In conclusion, the monocationic tracers [ 99m Tc(N)(PNP)(DBODC)] + exhibit high myocardial uptake in rats and dramatically high heart/lung and heart/liver ratios, suggesting that this novel class of perfusion agents could be conveniently employed to obtain heart images with superior imaging quality. (# 2002 Lippincott Williams & Wilkins)

Research paper thumbnail of Yap-(s)pet small animal scanner: quantitative results

IEEE Transactions on Nuclear Science, 2003

The University of Ferrara YAP-(S)PET scanner is currently being employed in small animal SPECT st... more The University of Ferrara YAP-(S)PET scanner is currently being employed in small animal SPECT studies, with 99 m Tc labeled radiotracers, with the goal of obtaining quantitative activity measurements from region of interest (ROI) analysis of reconstructed images of rats. The measurements will be compared directly with traditional ex vivo measurement of activity with gamma counters. To achieve this goal, the scanner was calibrated relative to a standard Isodose dose calibrator which was calibrated with various certified activity sources. The calibration factor K was defined as the ratio of the activity measured with the Isodose (MBq) and the image count rate (cps). We find K = 0 1346 0 0008 MBq cps, with good linearity over a wide range of activities (9-88 MBq). With the calibrated scanner we compared results of activity measurements from images of whole-rat heart acquisitions versus excised hearts. We found good agreement between the two measurements.

Research paper thumbnail of Rhenium(V) and Technetium(V) Nitrido Complexes with Mixed Tridentate π-Donor and Monodentate π-Acceptor Ligands

Inorganic Chemistry, 2012

Mixed-ligand [M(N)(SNS)(PPh(3))] complexes (M = Tc, Re) (1, 2) were prepared by reaction of the p... more Mixed-ligand [M(N)(SNS)(PPh(3))] complexes (M = Tc, Re) (1, 2) were prepared by reaction of the precursor [M(N)Cl(2)(PPh(3))(2)] with ligand 2,2'-dimercaptodiethylamine [H(2)SNS = NH(CH(2)CH(2)SH)(2)] in refluxing dichloromethane/ethanol mixtures. In these compounds, 2,2'-dimercaptodiethylamine acts as a dianionic tridentate chelating ligand bound to the [M≡N](2+) group through the two π-donor deprotonated sulfur atoms and the protonated amine nitrogen atom. Triphenylphosphine completes the coordination sphere, acting as a monodentate ligand. [M(N)(NS(2))(PPh(3))] complexes can assume two different isomeric forms depending on the syn and anti orientations of the hydrogen atom bound to the central nitrogen atom of the SNS ligand with respect to the M≡N moiety. X-ray crystallography of the syn isomer of complex 2 demonstrated that it has a distorted trigonal bipyramidal geometry with the nitrido group and the two sulfur atoms defining the equatorial plane, the phosphorus atom of the monophosphine and the protonated amine nitrogen of the tridentate ligand spanning the two reciprocal trans positions along the axis perpendicular to the trigonal plane. Synthesis of the analogous Tc derivatives with tris(2-cyanoethyl)phosphine, [Tc(N)(SNS)(PCN)] [(PCN = P(CH(2)CH(2)CN)(3)], required the preliminary preparation of the new precursor [Tc(N)(PCN)(2)Cl(2)](2) (3), which was prepared by reacting [n-NBu(4)][Tc(N)Cl(4)] with a high excess of PCN. The crystal structure of compound 3 consists of a noncrystallographic centrosymmetric dimer of Tc(V) nitrido complexes having an octahedral geometry. In this arrangement, the apical positions are occupied by two tris(2-cyanoethyl)phosphine groups and the equatorial positions by the nitrido group whereas the two Cl(-) anions and one cyano ligand belong to the other octahedral component of the dimer. By reacting the new precursor [Tc(N)(PCN)(2)Cl(2)](2) with the ligand H(2)SNS the complex [Tc(N)(SNS)(PCN)] (5) was finally obtained in acetonitrile solution. The new Tc(III) complex trans-[Tc(PCN)(2)Cl(4)][n-NBu(4)] (4) was also isolated from the reaction solution used for preparing complex 3 as side product and characterized by X-ray diffraction. The crystal structure of 4 consists of independent trans-[TcCl(4)(PCN)(2)](-) anions situated on crystallographic centers of symmetry and tetrabutylammonium cations in general positions.

Research paper thumbnail of Preparation and first biological evaluation of novel Re-188/Tc-99m peptide conjugates with substance-P

Applied Radiation and Isotopes, 2014

New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically ... more New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N](2+) (M=(99m)Tc, (188)Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands. The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N](2+) core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas the monodentate ligand was a tertiary phosphine. The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re≡N](2+) core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small-animal YAP(S)PET tomograph. New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high-yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re-188 radiopharmaceuticals exhibit identical biological properties.