99mTc Complexes Research Articles

⁹⁹mTc pyrene derivative complex causes double-strand breaks in dsDNA mainly through cluster-mediated indirect effect in aqueous solution.

Radiation therapy for cancer patients works by ionizing damage to nuclear DNA, primarily by creating double-strand breaks (DSB). A major shortcoming of traditional radiation therapy is the set of side effect associated with its long-range interaction with nearby tissues. Low-energy Auger electrons have the advantage of an extremely short effective range, minimizing damage to healthy tissue. Consequently, the isotope 99mTc, an Auger electron source, is currently being studied for its beneficial potential in cancer treatment. We examined the dose effect of a pyrene derivative 99mTc complex on plasmid DNA by using gel electrophoresis in both aqueous and methanol solutions. In aqueous solutions, the average yield per decay for double-strand breaks is 0.011±0.005 at low dose range, decreasing to 0.0005±0.0003 in the presence of 1 M dimethyl sulfoxide (DMSO). The apparent yield per decay for single-strand breaks (SSB) is 0.04±0.02, decreasing to approximately a fifth with 1 M DMSO. In methanol, the average yield per decay of DSB is 0.54±0.06 and drops to undetectable levels in 2 M DMSO. The SSB yield per decay is 7.2±0.2, changing to 0.4±0.2 in the presence of 2 M DMSO. The 95% decrease in the yield of DSB in DMSO indicates that the main mechanism for DSB formation is through indirect effect, possibly by cooperative binding or clustering of intercalators. In the presence of non-radioactive ligands at a near saturation concentration, where radioactive Tc compounds do not form large clusters, the yield of SSB stays the same while the yield of DSB decreases to the value in DMSO. DSBs generated by 99mTc conjugated to intercalators are primarily caused by indirect effects through clustering.

Effect of co-ligands on chemical and biological properties of 99mTc(III) complexes [99mTc(L)(CDO)(CDOH)2BMe] (L = Cl, F, SCN and N3; CDOH2 = cyclohexanedione dioxime)

Introduction99mTc-Teboroxime ([99mTcCl(CDO)(CDOH)2BMe]) is a member of the BATO (boronic acid adducts of technetium dioximes) class of 99mTc(III) complexes. This study sought to explore the impact of co-ligands on solution stability, heart uptake and myocardial retention of [99mTc(L)(CDO)(CDOH)2BMe] (99mTc-Teboroxime: L=Cl; 99mTc-Teboroxime(F): L=F; 99mTc-Teboroxime(SCN): L=SCN; and 99mTc-Teboroxime(N3): L=N3). MethodsRadiotracers 99mTc-Teboroxime(L) (L=F, SCN and N3) were prepared by reacting 99mTc-Teboroxime with NaF, NaSCN and NaN3, respectively. Biodistribution and imaging studies were carried out in Sprague–Dawley rats. Image quantification was performed to compare their heart retention and liver clearance kinetics. ResultsComplexes 99mTc-Teboroxime(L) (L=F, SCN and N3) were prepared in high yield with high radiochemical purity. All new radiotracers were stable for >6h in the kit matrix. In its HPLC chromatogram, 99mTc-Teboroxime showed one peak at ~15.5min, which was shorter than that of 99mTc-Teboroxime(F) (~16.4min). There were two peaks for 99mTc-Teboroxime(SCN) at 16.5 and 18.3min. 99mTc-Teboroxime(N3) appeared as a single peak at 18.4min. Their heart retention and liver clearance curves were best fitted to the bi-exponential decay function. The half-times of fast/slow components were 1.6±0.4/60.7±8.9min for 99mTc-Teboroxime, 0.8±0.2/101.7±20.7min for 99mTc-Teboroxime(F), 1.2±0.3/84.8±16.6min for 99mTc-Teboroxime(SCN), and 2.9±0.9/51.6±5.0min for 99mTc-Teboroxime(N3). The 2-min heart uptake followed the order of 99mTc-Teboroxime (3.00±0.37%ID/g)>99mTc-Teboroxime(N3) (2.66±0.01 %ID/g)≈99mTc-Sestamibi (2.55±0.46 %ID/g)>99mTcN-MPO (2.38±0.15 %ID/g). 99mTc-Teboroxime remains the best in first-pass extraction. The best image acquisition window is 0–5min for 99mTc-Teboroximine and 0–15min for 99mTc-Teboroximine(N3). ConclusionCo-ligands had significant impact on the heart uptake and myocardial retention of complexes [99mTc(L)(CDO)(CDOH)2BMe] (L=Cl, F, SCN and N3). Future studies should be directed towards minimizing the liver uptake and radioactivity accumulation in the blood vessels while maintaining their high heart uptake.

Imidazole stabilized [2+1] Re(I)/99mTc(I) complexes as isostructural nuclear and optical probes

Imidazole stabilized [2+1] Re(I)/99mTc(I) complexes as isostructural nuclear and optical probes

Enhancing chemical properties and stability of M(CO)3 (M=Re, 99mTc) complexes through ligand donor modifications

as antibodies that have slow pharmacokinetics. Thework to be presented involves the preparation of isostructural Tc and Re complexes of ligands derivatized with tetrazines which can be used to tag transcyclooctene modified biomolecules. A series of single amino acid chelate (SAAC) type ligands bearing tetrazines have been synthesized and methods to prepare their M(CO)3 complexes (M= Tc or Re) developed. Ligand synthesis, metal complexation studies, which includes preparation of luminescent Re complexes, along with biological evaluation of this new targeting strategy for technetium will be presented.

YIA1 Early Detection of the Process of Vascular Calcification with Spect-ct and Pet-ct using Novel Bone Seeking Radiopharmaceuticals in Rat Models

IntroductionVascular calcification is considered to be a significant predictor of coronary heart disease. It is also associated with serious clinical complications such as left ventricular hypertrophy and calcific uremic arteriolopathy....

Synthesis and initial biological evaluation of a novel Tc-99m radioligand as a potential agent for 5-HT1A receptor imaging

Abstract The synthesis, characterization and biological evaluation of N-Tolueneferrocenecarboxamide labeled with technetium-99m (99mTc-TTCC) is reported. Biological studies in Wistar rats showed the ability of 99mTc-TPCC to cross the intact blood-brain barrier. In vivo biodistribution indicated that this complex had good brain uptake (1.32% ID/g at 5 min and 0.64% ID/g at 60 min) and good retention (about 50% of the activity was retained in the brain at 60 min post-injection). Regional brain distribution study showed that hippocampus, where the 5-HT1A receptor density is high, had the highest uptake (0.73% ID/g at 5 min p.i.) and the cerebellum, where the 5-HT1A receptor density is low, had the lowest uptake (0.12% ID/gID/g at 5 min p.i.). After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 0.73% ID/g to 0.20% ID/g at 5 min p.i., while the cerebellum had no significant decrease. This result indicates that 99mTc complex has specific binding to 5-HT1A receptor.

Physicochemical studies of the reaction of 99mTc with 5,5′-diethyl barbituric acid, adenine, d-glucose and thiobarbituric acid at different temperatures

The reaction of 99mTc pertechnetate with 5,5′-diethyl barbituric acid, adenine, d-glucose and thiobarbituric acid at different temperatures was studied. The solvent effect on the electronic absorption spectra of the reactions was recorded. The reaction mixtures have been analyzed at different times using TLC and a radiodetctor to show the peaks at the plates. 99mTc pertechnetate is obtained from the Mo generators. It is difficult to separate the complexes in the solid state. The percentage of 99mTc involved in the complexes can be determined.Characterization of the 99mTc complexes as well as the determination of the extent of radiolabeling was done by thin layer chromatography using 0.9% NaCl solution as a solvent. The Rf value of 99mTcO4- is (≈1). The solvatochromism for the reaction of 99mTc with d-glucose was mainly affected by solute permanent dipole-solvent permanent dipole interaction, the dipolar interaction for the reaction of 99mTc with of 5,5′-diethyl barbituric acid and for the reaction of 99mTc with adenine and thiobarbituric was solute–solvent hydrogen bonding.

Clickable, Hydrophilic Ligand forfac-[MI(CO)3]+(M = Re/99mTc) Applied in anS-Functionalized α-MSH Peptide

The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction was used to incorporate alkyne-functionalized dipicolylamine (DPA) ligands (1 and 3) for fac-[MI(CO)3]+ (M = Re/99mTc) complexation into an α-melanocyte stimulating hormone (α-MSH) peptide analogue. A novel DPA ligand with carboxylate substitutions on the pyridyl rings (3) was designed to increase the hydrophilicity and to decrease in vivo hepatobiliary retention of fac-[99mTcI(CO)3]+ complexes used in single photon emission computed tomography (SPECT) imaging studies with targeting biomolecules. The fac-[ReI(CO)3(3)] complex (4) was used for chemical characterization and X-ray crystal analysis prior to radiolabeling studies between 3 and fac-[99mTcI(OH2)3(CO)3]+. The corresponding 99mTc complex (4a) was obtained in high radiochemical yields, was stable in vitro for 24 h during amino acid challenge and serum stability assays, and showed increased hydrophilicity by log P analysis compared to an analogous complex with nonfunctionalized pyridine rings (2a). An α-MSH peptide functionalized with an azide was labeled with fac-[MI(CO)3]+ using both click, then chelate (CuAAC reaction with 1 or 3 followed by metal complexation) and chelate, then click (metal complexation of 1 and 3 followed by CuAAC with the peptide) strategies to assess the effects of CuAAC conditions on fac-[MI(CO)3]+ complexation within a peptide framework. The peptides from the click, then chelate strategy had different HPLC tR’s and in vitro stabilities compared to those from the chelate, then click strategy, suggesting nonspecific coordination of fac-[MI(CO)3]+ using this synthetic route. The fac-[MI(CO)3]+-complexed peptides from the chelate, then click strategy showed >90% stability during in vitro challenge conditions for 6 h, demonstrated high affinity and specificity for the melanocortin 1 receptor (MC1R) in IC50 analyses, and led to moderately high uptake in B16F10 melanoma cells. Log P analysis of the 99mTc-labeled peptides confirmed the enhanced hydrophilicity of the peptide bearing the novel, carboxylate-functionalized DPA chelate (10a′) compared to the peptide with the unmodified DPA chelate (9a′). In vivo biodistribution analysis of 9a′ and 10a′ showed moderate tumor uptake in a B16F10 melanoma xenograft mouse model with enhanced renal uptake and surprising intestinal uptake for 10a′ compared to predominantly hepatic accumulation for 9a′. These results, coupled with the versatility of CuAAC, suggests this novel, hydrophilic chelate can be incorporated into numerous biomolecules containing azides for generating targeted fac-[MI(CO)3]+ complexes in future studies.

OAT3-Mediated Extrusion of the 99mTc-ECD Metabolite in the Mouse Brain

After administration of the (99m)Tc complex with N,N'-1,2-ethylenediylbis-L-cysteine diethyl ester ((99m)Tc-ECD), a brain perfusion imaging agent, the radioactive metabolite is trapped in primate brain, but not in mouse and rat. Here, we investigate the involvement of metabolite extrusion by organic anion transporter 3 (OAT3), which is highly expressed at the blood-brain barrier in mice, in this species difference. The efflux rate of radioactivity in the cerebrum of Oat3(-/-) mice at later phase was 20% of that of control mice. Thus, organic anion transporters in mouse brain would be involved in the low brain retention of radioactivity after (99m)Tc-ECD administration.

Synthesis of tripeptide derivatized cyclopentadienyl complexes of technetium and rhenium as radiopharmaceutical probes

We describe the syntheses of half-sandwich complexes of the type [(η(5)-Cp(CONH-R))M(CO)3] with M = Re or (99m)Tc. The R group represents different tri-peptides (tpe) which display high binding affinities for oligopeptide transporters PEPT2. The (99m)Tc complexes were prepared directly from [(99m)Tc(OH2)3(CO)3](+) and Diels-Alder dimerized, cyclopentadienyl derivatized peptides in water. This approach corroborates the feasibility of metal-mediated retro Diels-Alder reactions for the preparation of not only small molecules but also peptides carrying a [(η(5)-Cp)(99m)Tc(CO)3] tag. We synthesized the Diels-Alder product [(HCpCONH-tpe)2] from Thiele's acid [(η(5)-HCpCOOH)2] via double peptide coupling. The Re-complexes [(η(5)-CpCONH-tpe)Re(CO)3] were obtained by attaching [(Cp-COOH)Re(CO)3] directly to the N-terminus of peptides as received from SPPS. The authenticity of the (99m)Tc-complexes is confirmed by chromatographic comparison with the corresponding rhenium complexes, fully characterized by spectroscopic techniques.

Re and (99m)Tc complexes of BodP3--multi-modality imaging probes.

A fluorescent tridentate phosphine, BodP3 (2), forms rhenium complexes which effectively image cancer cells. Related technetium analogues are also readily prepared and have potential as dual SPECT/fluorescent biological probes.

99m Tc-sulfadimidine as a potential radioligand for differentiation between septic and aseptic inflammations

Sulfadimidine, a bacteriostatic drug blocking folic acid synthesis, was labeled with 99mTc producing a yield of about 90%. The optimum conditions required to obtain 90% yield of the 99mTc complex were as follows: 500 μg of sulfadimidine, 100 μg of SnCl2·2H2O, 5 min, room temperature (25 ± 1°C), pH 4 (0.5 M citrate buffer). The radiochemical purity of the labeled compound was determined using paper and thin-layer chromatography. Biodistribution study in normal mice showed high uptake of the 99mTc complex in stomach and intestine. The ratio of the uptake of the 99mTc complex in muscles infected with E. coli to that in normal mice was about 2, 1.5 and 1.4 at 15, 90, and 180 min post injection, respectively, whereas for the muscles inflamed with heat-killed E. coli or sterile turpentine oil the difference from the normal muscles was insignificant.

Synthesis and biological evaluation of fatty acids conjugates bearing cyclopentadienyl-donors incorporated [99mTc/Re(CO)3]+ for myocardical imaging

Four 99mTc-labeled fatty acid analogs, 1b, 2b, 3b, 4b were synthesized by a double ligand transfer reaction and theirs potential were investigated. The radiochemical yield of the radiotracers was from 11.7% to 30.3% (no decay corrected). Those compounds were found to be chemically stable when incubated in SD rat serum for 3 h at 37 °C. The biodistribution studies in mice showed that high radioactivity accumulated of Tc-99m complexes were observed, followed by moderate clearance from the heart. The maximum heart/blood ratio was 5.7 at 15 min postinjection of 1b. Metabolite analysis showed 1b was not metabolized by β-oxidation in the heart. These results suggest that 1b may be a promising radiotracer for evaluation of myocardial viability.

Synthesis, structural characterization and radiochemistry of di- and tricarbonyl Re(I) and 99mTc(I) complexes with 8-hydroxyquinoline or 8-mercaptoquinoline and triphenylphosphine

In this work, we focused on the development of mixed ligand technetium and rhenium complexes of the general formula fac-[99mTc/Re(CO)3(PPh3)(ox/tq)] and cis, trans-[99mTc/Re(CO)2(PPh3)2(ox/tq)] where 8-hydroxyquinoline (oxH) and 8-mercaptoquinoline (tqH) act as [NO] and [NS] bidentate ligands. The synthesis of rhenium complexes fac-[Re(CO)3(PPh3)(ox/tq)] Re3/Re4 was conducted by reacting oxH or tqH and triphenylphosphine with fac-(NEt4)2[Re(CO)3Br3] (1) or by reacting triphenylphosphine with the dimer complexes fac-[Re(CO)3(ox/tq)]2Re1/Re2. The synthesis of the rhenium complexes cis, trans-[Re(CO)2(PPh3)2(ox/tq)] Re5/Re6 was conducted either by reacting 1 with oxH/tqH in equimolar amounts and triphenylphosphine in excess or by reacting oxH/tqH with the precursor mer, trans-[Re(CO)3(PPh3)2Cl]. All the complexes were characterized by IR, NMR and X-ray crystallography. The analogous 99mTc complexes were prepared by reacting oxH/tqH and PPh3 with the precursor fac-[99mTc(CO)3(OH2)3]+ (2). When the reaction mixture was left at rt for 2h the monophosphino complexes fac-[99mTc(CO)3(PPh3)(ox/tq)] 99mTc3/99mTc4 were formed, while by applying heating at 75°C for 30min the dicarbonyl complexes cis, trans-[99mTc(CO)2(PPh3)2(ox/tq)] 99mTc5/99mTc6 were formed quantitatively. The 99mTc complexes were identified by HPLC chromatographic comparison with the analogous rhenium complexes and their stability was studied.

Target-specific Tc(CO)3-complexes for in vivo imaging

In recent years, the remarkable characteristics of the organometallic precursor fac-[M(CO)3(H2O)3]+ (M = Re, Tc) introduced by Alberto and co-workers brought renewed interest to the development of low-oxidation 99mTc-based radioactive probes. Considering our interest in the design of target-specific radioactive probes for SPECT-imaging and targeted systemic radiotherapy, we have been involved in the study of the chemistry of fac-[M(CO)3]+ (M = Re, Tc) with chelators combining a pyrazolyl unit with aliphatic amines and/or carboxylic acids or thioethers. This review describes our research efforts in the field, giving particular emphasis to the biological properties of Re(I) and 99mTc(I) complexes anchored by those type of chelators. We aim to highlight the versatility of the pyrazolyl-containing chelators, which allowed the successful labeling of a wide range of relevant biomolecules, spanning from small lipophilic organic molecules, such as quinazoline derivatives or DNA-binders, to tumor-seeking peptides for in vivo receptor targeting. Noteworthy is also the possibility of labeling polymeric nanoparticles based on dextran for sentinel lymph node detection (SLND), which has been one of our most successful achievements in recent years. These radiolabeled nanoparticles allowed the visualization of the SLN accurately at the preclinical level.

Modification of PLGA Nanoparticles for Improved Properties as a 99mTc-Labeled Agent in Sentinel Lymph Node Detection

We have earlier reported on the possible application of poly [lactide (co-glycolide)] (PLGA) nanoparticles of suitable size to serve as a (99m)Tc-labeled diagnostic tracer in sentinel lymph node detection (SLND). Additional efforts have now been made to improve both the radiolabeling yield and the biological efficacy by modifying the PLGA particles. Two approaches were taken, one based on in situ loading of mebrofenin inside PLGA nanoparticles and the second one based on functionalization of existing terminal carboxylic acid groups on the nanoparticle surface with p-aminobenzyl diethylenetriamine pentaacetic acid (p-NH2-Bz-DTPA) for enhanced availability of functional groups suitable for (99m)Tc complexation. The modified PLGA derivatives were purified and characterized. Radiolabeling of the modified PLGA nanoparticles was carried out with (99m)Tc using stannous chloride as the reducing agent. Mebrofenin encapsulated PLGA nanoparticles (mebrofenin-PLGA) did not show any significant improvement in the radiolabeling yield in comparison to the earlier reported "plain" PLGA nanoparticles, probably due to inaccessibility of the mebrofenin moiety to (99m)Tc upon encapsulation. DTPA-conjugated PLGA nanoparticles (DTPA-PLGA) showed appreciable improvement in radiolabeling yield under more moderate reaction conditions and better stability. In the biological evaluation performed in Wistar rat model, (99m)Tc-DTPA-PLGA nanoparticles showed a considerable increase in uptake in the sentinel node and the percentage popliteal extraction of the preparation was also higher. (99m)Tc-mebrofenin-PLGA did not show any improvement in SLN uptake over plain PLGA nanoparticles. The above results suggest that surface modification of PLGA by covalently coupling DTPA to PLGA nanoparticles prior to (99m)Tc labeling appears to be a superior approach to achieve a suitable (99m)Tc-labeled PLGA nanoparticle preparation for SLND.

Design and Development of 99mTc-‘4+1’-Labeled Dextran-Mannose Derivatives as Potential Radiopharmaceuticals for Sentinel Lymph Node Detection

The synthesis, labeling, and biological evaluation of a dextran derivative (DCM-30-iso) as potential radiopharmaceutical for sentinel lymph node imaging is presented. DCM-30-iso bears mannose as active moiety and isocyanide as ligand for technetium through the formation of a '4+1' Tc(III) mixed-ligand complex. A second derivative without mannose (DC-25-iso) was also prepared and evaluated as control. DCM-30-iso and DC-25-iso were synthesized from dextran in four steps (>50% overall yield) and characterized by spectroscopic methods. Labeling with (99m)Tc was achieved by reaction with 2,2',2''-nitrilotris(ethanethiol) and (99m)Tc-EDTA. Radiochemical purity was above 90% and was stable for at least 4 hours postlabeling at 37°C. The identity of the (99m)Tc complex was established through comparative HPLC studies using the well-characterized analogous Re-DC-25-iso complex. Biodistribution and imaging experiments of (99m)Tc-DCM-30-iso showed high uptake in the popliteal lymph node, which could be blocked with preinjection of mannose, and very low uptake in other nodes and organs. The nonmannosylated (99m)Tc-DC-25-iso derivative showed negligible uptake in all lymph nodes. The novel dextran-mannose derivative DCM-30-iso can be successfully labeled with (99m)Tc to give a well-characterized '4+1' complex with favorable biological properties as sentinel lymph node imaging agent.

(Cp-R)M(CO)3] (M= Re or 99mTc) Conjugates for Theranostic Receptor Targeting

Cyclopentadienyl complexes of 99mTc became accessible via a retro Diels-Alder synthetic approach of dimerized cyclopentadiene derivatives. So far, this approach was limited to derivatives comprising a carboxylic acid group, directly conjugated to the Cp-ring, leading to complexes [(C5H5COOH)99mTc(CO)3] and [(C5H5CONH-R)99mTc(CO)3], respectively. The introduction of an -NCO group via Curtius rearrangement and subsequent in situ reactions with alcohols or amines gave [(C5H5NHCO-OR)2] and [(C5H5NHCO-NHR)2]. To increase the spacer lengths between the Cp-ring and the functional groups, methylene and ethylene spacers were introduced to yield C5H5-CH2COOH and C5H5-C2H4COOH respectively. The latter Cp-derivatives reacted with [99mTcO4)]- and in the presence of CO releasing/reducing agents to the corresponding [(C5H5-spacer-COOH)99mTc(CO)3] complexes. The carboxylato groups can be derivatized with targeting functions, leading to structurally altered receptor binding complexes, with 99mTc for imaging and with rhenium for therapy. The nature of the 99mTc complexes was assessed by HPLC comparison with the corresponding rhenium compounds.

Mono- and dicationic Re(I)/99mTc(I) tricarbonyl complexes for the targeting of energized mitochondria

The enhanced negative mitochondrial membrane potential of tumor cells can increase the cell accumulation of triphenylphosphonium (TPP) derivatives, which prompted us to investigate TPP-containing Re(I)/99mTc organometallic compounds as probes for in vivo targeting of energized mitochondria. Novel compounds (Re1–Re4/Tc1–Tc4) were obtained with bifunctional chelators of the pyrazole-diamine (N,N,N-donors) and pyrazole-aminocarboxylic (N,N,O-donors) type, functionalized with TPP pharmacophores that have been introduced at the central amine of the chelators using different spacers. In this way, dicationic (Re1–Re2, Tc1–Tc2) and monocationic (Re3–Re4, Tc3–Tc4) complexes with variable lipophilicity were synthesized. The 99mTc complexes (Tc1–Tc4) are highly stable under physiological conditions and their chemical identification was done by HPLC comparison with the Re congeners (Re1–Re4), which were fully characterized by common analytical techniques (electrospray ionization mass spectrometry (ESI-MS), IR, multinuclear NMR). The in vitro biological evaluation of Tc1–Tc4 was performed in a panel of human tumor cell lines (PC-3, MCF-7 and H69), including cell lines overexpressing P-glycoprotein (MCF-7/MDR1 and H69/Lx4), and in isolated mitochondria. All the tested complexes showed a low to moderate cellular and mitochondrial uptake and did not undergo significant P-glycoprotein (Pgp)-mediated efflux processes. In particular, the dication Tc2 and the monocation Tc4 presented the highest cellular and mitochondrial uptake. Their cellular uptake was shown to depend on the mitochondrial (Δψm) and plasma membrane (Δψp) potentials. Altogether, the biological properties of these compounds suggest that they might be relevant for the design of radioactive metalloprobes for in vivo targeting of mitochondria.

A new bifunctional tridentate NSN ligand leading to cationic tricarbonyl fac-[M(NSN)(CO)3]+ (M = Re, 99mTc) complexes

The synthesis and characterization of the new NSN tridentate bifunctional chelating agent 3-[2-(2′-pyridin-2-yl-ethylsulfanyl)ethylamino] propionic acid (as its hydrochloric salt, 1) and of its corresponding rhenium complex fac-[Re(NSN)(CO)3]+, 2, is described. Both compounds were characterized by elemental analysis, IR and NMR spectroscopies and X-ray crystallography. In complex 2 the coordination geometry around rhenium is distorted octahedral with the NSN atoms participating in the coordination sphere while the carboxylate group remains free. At tracer level, the analogous complex fac-[99mTc(NSN)(CO)3]+, 3, was obtained in high yield by reacting ligand 1 with the fac-[99mTc(H2O)3(CO)3]+ precursor at pH 6.5. The structure of 3 was established by HPLC comparison to the prototype rhenium complex 2. Complex 3 is stable in solution as well as in the presence of strongly coordinating agents like histidine or cysteine. Our data indicate that ligand 1 can be used as a bifunctional NSN chelating agent in the design of potential 99mTc-radiopharmaceuticals.