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The β- emitter, rhenium-188 (188Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares chemical similarities with its congener element technetium, whose nuclear isomer technetium-99m (99mTc) is the current workhorse of diagnostic nuclear medicine. The differences between these two elements have a significant impact on the radiolabelling methods and should always receive critical attention. This review aims to highlight what needs to be considered to design a successful radiopharmaceutical incorporating 118Re. Some of the most effective strategies for preparing therapeutic radiopharmaceuticals with 188Re are illustrated and rationalized using the concept of the inorganic functional group (core) and a simple ligand field theoretical model combined with a qualitative definition of frontiers orbitals. Of special interest are the Re(V) oxo and Re(V) nitrido functional groups. Suitable ligands for binding to these cores are discussed, successful clinical applications are summarized, and a prediction of viable future applications is presented. Rhenium-188 decays through the emission of a high energy beta particle (2.12 MeV max energy) and a half-life of 16.9 h. An ideal biological target would therefore be a high-capacity target site (transporters, potential gradients, tumour microenvironment) with less emphasis on saturable targets such as overexpressed receptors on smaller metastases. ispartof: MOLECULES vol:28 issue:3 ispartof: location:Switzerland status: published

Rapid imaging acquisition, high spatial resolution and sensitivity, powered by advancements in solid-state detector technology, are significantly changing the perspective of single photon emission tomography (SPECT). In particular, this evolutionary step is fueling a rediscovery of technetium-99m, a still unique radionuclide within the nuclear medicine scenario because of its ideal nuclear properties and easy preparation of its radiopharmaceuticals that does not require a costly infrastructure and complex procedures. Scope of this review is to show that the arsenal of technetium-99m radiopharmaceuticals is already equipped with imaging agents that may complement and integrate the role played by analogous tracers developed for positron emission tomography (PET). These include, in particular, somatostatin (SST) and prostate-specific membrane antigen (PSMA) receptor targeting agents, and a number of peptide-derived radiopharmaceuticals. Additionally, these recent technological developments, combined with new myocardial perfusion tracers having more favorable biodistribution and pharmacokinetic properties as compared to current commercial agents, may also reinvigorate the prevailing position still hold by technetium-99m radiopharmaceuticals in nuclear cardiology.

The purpose of this work was to further expand the chemistry of mixed technetium nitrido-peroxo complexes, a still poorly explored class of compounds containing the Tc(VII) moiety, [99gTc][Tc(N)(O2)2]. A number of novel complexes of the formula [99gTc][Tc(N)(O2)2(L)] with bidentate ligands (L) (where L = deprotonated alanine, glycine, proline) were prepared by reacting a solution of nitrido-technetic(VI) acid with L in the presence of a source of H2O2. Alternatively, the complex [99gTc][Tc(N)(O2)2X]&minus, (X = Cl, Br) was used as a precursor for substitution reactions where the halogenide ion was replaced by the bidentate ligand. The new complexes were characterized by elemental analysis and mass spectroscopy. The preparation of the analogous [99mTc][Tc(N)(O2)2] moiety, radiolabeled with the metastable isomer Tc-99m, was also studied at a no-carrier-added level, using S-methyl-N-methyl-dithiocarbazate as the donor of the nitrido nitrogen atoms.

Background: the gamma-emitting radionuclide Technetium-99m (99mTc) is still the workhorse of Single Photon Emission Computed Tomography (SPECT) as it is used worldwide for the diagnosis of a variety of phatological conditions. 99mTc is obtained from 99Mo/99mTc generators as pertechnetate ion, which is the ubiquitous starting material for the preparation of 99mTc radiopharmaceuticals. 99Mo in such generators is currently produced in nuclear fission reactors as a by-product of 235U fission. Here we investigated an alternative route for the production of 99Mo by irradiating a natural metallic molybdenum powder using a 14-MeV accelerator-driven neutron source. Methods: after irradiation, an efficient isolation and purification of the final 99mTc-pertechnetate was carried out by means of solvent extraction. Monte Carlo simulations allowed reliable predictions of 99Mo production rates for a newly designed 14-MeV neutron source (New Sorgentina Fusion Source). Results: in traceable metrological conditions, a level of radionuclidic purity consistent with accepted pharmaceutical quality standards, was achieved. Conclusions: we showed that this source, featuring a nominal neutron emission rate of about 1015 s−1, may potentially supply an appreciable fraction of the current 99Mo global demand. This study highlights that a robust and viable solution, alternative to nuclear fission reactors, can be accomplished to secure the long-term supply of 99Mo.

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [99mTc][TcO4]- ubiquitously employed for the production of 99mTc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction 100Mo(p,2n)99mTc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of 99Mo/99mTc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron. On this ground, an outline of the essential steps that should be implemented for setting up a hospital radiopharmacy aimed at the occasional production of Tc-99m by a small cyclotron is discussed. These include (1) target production, (2) irradiation conditions, (3) separation/purification procedures, (4) terminal sterilization, (5) quality control, and (6) Mo-100 recovery. To address these issues, a comprehensive technology for cyclotron-production of Tc-99m, developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL-INFN), will be used as a reference example.

Technetium-99m (Tc-99m) has long been a mainstay in clinical nuclear medicine, primarily monitoring biological processes in the heart, kidney, liver, and brain. More recently, Tc-99m chelates have been used as the reporter in targeted nuclear medicine probes that monitor changes in specific protein expression products. The strengths remain the inexpensive source of Tc-99m from the Mo-99/Tc-99m generator, its rich chemistry, high-yield kit formulation, and its widespread availability. Hardware and software advances, such as OSEM reconstructions with scatter and attenuation corrections, have led to quantitation of the injected radioactivity in terms of kBq/cm.

Introduction New 188Re and 99mTc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N]2+ (M=99mTc, 188Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands. Methods 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. Conclusion 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.

Reactions of dppf with labile technetium and rhenium precursors such as [M(N)Cl 4 ] − and [M(NPh)Cl 3 (PPh 3 ) 2 ] yield the monomeric mono-substituted [M(N)Cl 2 (dppf)] and [M(NPh)Cl 3 (dppf)] complexes, where the diphosphinoferrocenyl fragment coordinates on the equatorial plane of a distorted square pyramid or of a distorted octahedron, respectively.

A new molecular metallic fragment for labeling biologically active molecules with 99mTc and 188Re is described. This system is composed of a combination of tridentate π-donor and monodentate π-acceptor ligands bound to a [M Ξ N]2+ group (M = (99m)Tc, 188Re) in a pseudo square-pyramidal geometry. A simple structural model of the new metallic fragment was obtained by reacting the ligand 2, 2'-iminodiethanethiol [H2NS2 = NH(CH2CH2SH)2] and monodentate tertiary phosphines with the [M Ξ N]2+ group (M = (99m)Tc, (188)Re). In the resulting complexes (dubbed3+1complexes), the tridentate ligand binds the [M Ξ N]2+ core through the two deprotonated, negatively charged, thiol sulfur atoms and the neutral, protonated, amine nitrogen atom. The residual fourth position of the five-coordinated arrangement is occupied by a phosphine ligand. The chemical identity of these model (99m)Tc and (188)Re compounds was established by comparison with the chromatographic properties of the corresponding complexes obtained at the macroscopic level with the long-lived (99)Tc and natural Re isotopes. The investigation was further extended to comprise a series of ligands formed by simple combinations of two basic amino acids or pseudo-amino acids to yield potential tridentate chelating systems having [S, N, S] and [N, N, S] as sets of π-donor atoms. Labeling yields and in vitro stability were investigated using different ancillary ligands. Results showed that SNS-type ligands afforded the highest labeling yields and the most robust 3+1 nitrido complexes with both (99m)Tc and (188)Re. Thus, the new chelating system can be conveniently employed for labeling peptides and other biomolecules with the [M Ξ N]2+ group.

Technetium 99m-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) (99mTcN-NOET) is a new neutral cardiac perfusion imaging agent that has been shown to have very high uptake and retention in vitro. The purpose of this study was to determine the clearance kinetics of 99mTcN-NOET in control, ischemic-reperfused, and membrane-disrupted myocardium.After a 100 microCi (3.7 x 10(6) Bq) bolus of 99mTcN-NOET was injected, myocardial clearance was monitored for 1 hour by the use of a sodium iodide detector in 30 isolated, Krebs-Henseleit (KH) perfused rat hearts. Seven hearts were used as controls (group 1). In seven ischemic-reperfused hearts, tracer administration and uptake was followed by 30 minutes of no flow and 1 hour of reflow (group 2). In six additional ischemic-reperfused hearts, tracer administration was followed by deprivation of flow for 1 hour followed by 1 hour of reflow (group 3). Six hearts were perfused with a 0.5% Triton X-100 KH perfusate for 1 hour (group 4). Four hearts were perfused with KH for 10 minutes, followed by cyanide for 10 minutes (group 5). This cycle was repeated three times. Activities remaining in each heart at the end of each experiment were quantitated, and activity at peak uptake was calculated. The 99mTcN-NOET myocardial clearance was near linear in the control (0.6 +/- 0.4) and both ischemic-reperfused groups with virtually no fractional clearance (1.2% +/- 0.6% and 2.1% +/- 0.6%, respectively; p = NS). In the Triton X-100 membrane-disrupted hearts, clearance was substantial (94.2% +/- 4.0%; p0.0001 compared with the control and ischemic-reperfused groups). Cyanide treatment produced rapid clearance, which was arrested by a return to the standard KH perfusate. Peak uptake as a percentage of injected dose was 74.9% +/- 1.4% for all groups combined.Thus 99mTcN-NOET has extremely high myocardial retention after 1 hour in normal myocardium and is not significantly affected by ongoing myocardial ischemia or reperfusion injury in this model. Clearance is increased markedly in extreme conditions of membrane disruption. These data are consistent with the concept that 99mTc-NOET is localized predominantly in or on cell membranes. 99mTcN-NOET is a promising, new myocardial perfusion imaging agent that exhibits a stable myocardial distribution in the setting of acute developing injury.

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.

The reaction of pertechnetate with the S-methyl ester of dithiocarbazic acid, H2N–NR–C(S)SCH3(R = H or CH3), in the presence of HCl and triphenylphosphine, affords the technetium(V) nitrido complex [TcNCl2(PPh3)2] in high yield. Derivatives of S-methyl dithiocarbazate of the type R1(R2)CN–NR3–C(S)SCH3, where R1=o-C6H4OH, C6H5, or CH3, R2= H or CH3, and R3= H or CH3, behave as sources of N3– groups, giving rise to a variety of technetium complexes containing the TcN multiple bond. These reactions apply equally well to the preparation of technetium-99m radiopharmaceuticals containing the TcN group, at the non-carrier-added level of nuclear medicine.

The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine–dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene–S-cysteine–dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/μg.

Our purpose was to evaluate the safety profile and biodistribution behavior in healthy human volunteers of the new myocardial perfusion tracer bis[(dimethoxypropylphosphanyl)ethyl]ethoxyethylamine N,N′-bis(ethoxyethyl)dithiocarbamato nitrido technetium(V) (99mTc-N-DBODC). Methods: Ten healthy male volunteers were injected with 99mTc-N-DBODC under both stress and rest conditions. Anterior and posterior planar γ-camera images were collected at 5, 30, 60, 240, and 1,440 min after injection, with organ uptake quantified by region-of-interest analysis. Tracer kinetics in body fluids were determined by collecting blood and urine samples at different time points. Results: After injection, 99mTc-N-DBODC showed significant accumulation in the myocardium and prolonged retention. Under rest conditions, uptake in the heart, lungs, and liver at 5 min after injection was 1.67% ± 0.13%, 1.16% ± 0.07%, and 10.85% ± 1.72%, respectively, of administered activity. Under stress conditions, heart uptake was significantly higher (2.07% ± 0.22%). Radioactivity in the liver decreased to 3.64% ± 0.98% and 2.37% ± 0.48% at 60 and 240 min, respectively, after injection. This rapid liver clearance led to favorable heart-to-liver ratios, reaching values of 0.74 ± 0.13 at rest and 1.26 ± 0.28 during exercise 60 min after tracer administration. Radiation dose estimates were comparable to those obtained with other myocardial perfusion cationic compounds. Conclusion: The high uptake in the myocardium and the fast liver washout of 99mTc-N-DBODC will allow SPECT images of the left ventricle to be acquired early and with excellent quality.

The reaction of pertechnetate with the S-methyl ester of dithiocarbazic acid, H2N–NR–C(S)SCH3(R = H or CH3), in the presence of HCl and triphenylphosphine, affords the technetium(V) nitrido complex [TcNCl2(PPh3)2] in high yield. Derivatives of S-methyl dithiocarbazate of the type R1(R2)CN–NR3–C(S)SCH3, where R1=o-C6H4OH, C6H5, or CH3, R2= H or CH3, and R3= H or CH3, behave as sources of N3– groups, giving rise to a variety of technetium complexes containing the TcN multiple bond. These reactions apply equally well to the preparation of technetium-99m radiopharmaceuticals containing the TcN group, at the non-carrier-added level of nuclear medicine.

Mono-cationic nitrido heterocomplexes of general formula [M(N)(DTC)(PNP)]+ (where M is 99Tc or Re, DTC is the mono-anionic form of a dithiocarbamate ligand, and PNP is a diphosphane ligand with a tertiary amine-containing five-membered spacer) were prepared by ligand-exchange reactions with the labile precursors [M(N)Cl2(PPh3)2] in dichloromethane/alcohol mixtures. The molecular structure of the representative rhenium complex [Re(N)(dedc)(pnp2)][PF6] (1) displays a distorted, square-pyramidal geometry with the dithiocarbamate sulfur and the diphosphane phosphorus atoms spanning the four coordination positions on the equatorial plane. If the additional interactions between the nitrido nitrogen and the weakly bonded transN-diphosphane heteroatom, the molecular geometry can be viewed as pseudo-octahedral. The structure in solution, as established by multinuclear NMR spectroscopy and ESI spectrometry, is monomeric, and identical to that shown in the solid state. Replacement of the phenyl groups on the phosphorous atoms in complexes 1, 2, 5, and 6 with alkyl groups modified neither the course of the reaction nor the composition of the resulting complexes. These results, together with the observation that no symmetrical complexes containing two identical bidentate ligands were produced in these reactions, strongly supports the conclusion that a mixed coordination sphere, composed by a combination of π-donor and π-acceptor atoms around the [M≡N]2+ group, constitutes a highly stable system. Compounds containing dangling alkyl-substituted groups in the outer sphere (3, 4, 7, and 8) were fully characterized by multinuclear NMR spectroscopy and ESI mass spectrometry. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

A new biomolecule labeling method that utilizes the [99mTc(N)(PNP)]2+m metal fragment is presented. Thus, a series of nitrido mixed-ligand M(V) complexes (M = 99mTc, 99gTc, Re), [M(N)(Ln)(PNP)], where Ln is the dianionic form of a dithiolate or substituted-dithiolate ligand and PNP is an aminodiphosphine, is described. 99mTc complexes can be prepared using either a two-step or a three-step procedure starting from generator-eluted pertechnetate through a pre-reduced mixture of [99mTc(N)] containing species, followed by contemporary or sequential addition of the relevant dithiolate and aminodiphosphine. The reaction of 2,3-dimercapto propionic acid (H2L1) with [Tc(N)(PNP)]2+ was investigated in detail. It was found that this bidentate ligand coordinated the metal fragment through the [S-,S-] donor atom pair, to yield neutral mixed-ligand complexes [99mTc(N)(L1)(PNP)] in high specific activity. The additional carboxylic functional group was not involved in metal coordination, thus remaining available for conjugation to target-specific molecules. Dithiolates incorporating pendant functional group(s) gave rise to a 1:1 diastereoisomeric mixture of syn-[M(N)(Ln)(PNP)] and anti-[M(N)(Ln)(PNP)] derivatives, depending on the relative orientation of the dithiolate substituent(s) with respect to the terminal nitrido group, and no isomeric conversion was detected. 99mTc species had been proven to be identical with the 99gTc complexes prepared at the macroscopic level by comparison of the corresponding radiometric and UV/vis HPLC profiles. Challenge experiments with cysteine or glutathione indicated that these physiological agents had no effect on the stability of this class of mixed-ligand 99mTc-complexes. Biodistribution studies in rats of selected 99mTc-complexes showed a rapid clearance from the blood and tissues after 60 min. p.i..

A new labeling approach for incorporating bioactive peptides into a technetium-99m coordination complex is described. This method exploits the chemical properties of the novel metal-nitrido fragment [99mTc(N)(PXP)]2+, composed of a terminal Tc[triple bond] N multiple bond bound to an ancillary diphosphine ligand (PXP). It will be shown that this basic, molecular building block easily forms in solution as the dichloride derivative [99mTc(N)(PXP)Cl2], and that this latter complex selectively reacts with monoanionic and dianionic, bidentate ligands (YZ) having soft, pi-donor coordinating atoms to afford asymmetrical nitrido heterocomplexes of the type [99mTc(N)(PXP)(YZ)]0/+ without removal of the basic motif [99mTc(N)(PXP)]2+. The reactions of the amino acid cysteine was studied in detail. It was found that cysteine readily coordinates to the metal fragment [99mTc(N)(PXP)]2+ either through the [NH2, S-] pair of donor atoms or, alternatively, through the [O-, S-] pair, to yield the corresponding asymmetrical complexes in very high specific activity. Thus, these results were conveniently employed to devise a new, efficient procedure for labeling short peptide sequences having a terminal cysteine group available for coordination to the [99mTc(N)(PXP)]2+ fragment. Examples of the application of this novel approach to the labeling of the short peptide ligand H-Arg-Gly-Asp-Cys-OH (H(2)1) and of the peptidomimetic derivative H-Cys-Val-2-Nal-Met-OH (H2) will be discussed.

New Tc-99m radiopharmaceuticals with the ligand ( o -hydroxyphenyl)diphenylphosphine have been prepared and their biodistributions evaluated in rats. The monoxo Tc(V) complex [ 99m Tc(O)Cl(PO) 2 ], the Tc(IV) complex [ 99m Tc(OH) 2 (PO) 2 ], the Tc(III) complex [ 99m Tc(PO) 3 ], and the nitrido Tc(V) complex [ 99m Tc(N)(PO) 2 ] have been characterized by TLC and HPLC chromatography, and their chemical structure elucidated by comparison with the corresponding complexes obtained using the β-emitting isotope Tc-99g. Biodistribution studies of these complexes have been carried out in rats.

The symmetrical complexes [99mTc][TcN(R2PS2)2] [R = CH3, CH2CH3, CH2CH2CH3, CH2(CH3)2], and the unsymmetrical complex [99mTc][TcN(Me2PS2)(Et2PS2)] have been prepared, at tracer level, through a two-step procedure involving the preliminary formation of a prereduced technetium nitrido intermediate followed by substitution reaction onto this species by the appropriate dithiophosphinate ligand [R2PS2]Na. The chemical identity of the resulting complexes have been established by comparison with the corresponding 99Tc-analogs prepared, at macroscopic level, by reacting the complex [99TcNCl4] [n-Bu4N] (n-Bu = n-butyl) with an excess of ligand in methanol, and characterized by elemental analyses and spectroscopic techniques. The complexes are neutral and lipophilic, and possess a square pyramidal geometry, with an apical Tc identical to N group and two dithiophosphinate ligands spanning the four positions on the basal plane through the four sulfur atoms of the > PS2 group. In vitro studies showed that these radiopharmaceuticals are stable in solution and that their chemical identity was not altered after incubation with rat blood. Biodistribution studies have been carried out in rats and primates. The results demonstrate that these compounds are significantly retained into the brain of these animals for a prolonged time. Planar gamma camera images have been obtained in monkeys showing a good visualization of the cerebral region. However, the existence of persistent blood activity yields a brain/blood ratio lower than that observed with other 99mTc-based brain perfusion imaging agents.

The synthesis, characterization and electrochemical behaviour of neutral [TcN(noet)2][noet = Et(EtO)N–CS2–], the first technetium(V) nitrido complex currently under preliminary clinical evaluation for myocardial perfusion, are reported.

The synthesis, characterization and electrochemical behaviour of neutral [TcN(noet)2][noet = Et(EtO)N–CS2–], the first technetium(V) nitrido complex currently under preliminary clinical evaluation for myocardial perfusion, are reported.

The complex [Tc(PPh3)2(CO)3Cl] reacts with the lithium salt of amido-carboxylato- and thiazolato-derivatives to give the new complexes (Ar= C6H4Me-p or C6H4OMe-p), [Tc(PPh3)2(CO)2(amt1,2)] [amt1=anion of 2-(methylamino)thiazole; amt2=anion of 2-4-methoxyphenylamino(thiazole)] and [Tc(PPh3)2(CO)2- (R = Ph2CH, PhCH2 or CCl3). The compounds have been characterized by elemental analysis, and i.r. and1H n.m.r. spectra.

Preparation et caracterisation spectrometrique des complexes du titre. Etude radiocristallographique du complexe de technetium(V)

Le (N-salicylidene-D-glucosimato)(salicylaldehydato) oxotechnetium(V) cristallise dans le systeme orthorhombique avec le groupe d'espace P2 1 2 1 2 1 . Affinement de la structure jusqu'a 0,054. L'atome Tc se trouve dans un environnement de coordination octaedrique deforme, les 3 atomes donneurs du coordinat base de Schiff occupant le plan normal a la liaison Tc=0

A novel class of technetium-99m radiopharmaceuticals showing high heart uptake is described. These complexes were prepared through a simple and efficient procedure, and their molecular structure fully characterized. They are formed by a terminal Tc≡N multiple bond and two bidentate phosphine-thiol ligands [R 2 P-(CH 2 ) n SH, n=2,3] coordinated to the metal ion through the neutral phosphorus atom and the deprotonated thiol sulfur atom. The resulting geometry was trigonal bipyramidal. Biodistribution studies were carried out in rats. The complexes exhibited high initial heart uptake and elimination through liver and kidneys. The washout kinetic from heart was dependent on the nature of the lateral R groups on the phosphine-thiol ligands. When R = phenyl , heart activity was rapidly eliminated within 10–20 min. Instead, when R = tolyl , cyclohexyl , persistent heart uptake was observed. Extraction of activity from myocardium tissue showed that no change of the chemical identity of the tracer occurred after heart uptake. On the contrary, metabolization to more hydrophilic species occurred in liver and kidneys.

Preparation du complexe sulfuro du titre a partir de la reaction de [MoCl 2 (HB(pz) 3 )], M=Tc, Re avec B 2 S 3