Synthesis, characterization and biological evaluation of a novel “3 + 1” mixed ligand 99mTc complex having an aliphatic thiol as coligand

Rey, Ana; Papadopoulos, Minas; León, Elsa; Mallo, L.; Pirmettis, Y.; Manta, Eduardo; Raptopoulou, Catherine P.; Chiotellis, E.; León, A.

doi:10.1016/s0969-8043(00)00285-2

Cited by 7 publications

(9 citation statements)

References 19 publications

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“…The biodistribution experiments with the 99m Tc complex were performed in normal female mice to ascertain the in vivo distribution profile of the radiotracers according to [16]. The animal biodistribution experiments were performed in accordance with institutional, national, and international regulations governing the safe and humane use of laboratory animals in research.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and characterization of a {ReO}3+ complex with S- and N-donor ligands and of its 99m Tc analog

Alhokbany

2012

Radiochemistry

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A novel mixed-ligand 99m Tc complex with mercaptobenzothiazole (mer) as ligand and aminothiazole (amino) as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using 99m Tc-gluconate as precursor and a coligand/ligand ratio of 5. Under these conditions, the labeling yield was over 97% and the major product with radiochemical purity >97% was isolated by HPLC and used for biological evaluation. The reaction of [ReO(Citrate) 2 ] -with mer and amino in hot MeOH yields [ReO(mer)(amino)OH(H 2 O) 2 ]. The DFT study demonstrated that the complex contains distorted octahedral ReO(V). The Re coordination sphere consists of the terminal oxo group, the S donor atom of the deprotonated mer, the N atom of the deprotonated amino, OH group, and two water molecules. Biodistribution in mice demonstrated early brain uptake, fast blood clearance, and excretion through hepatobiliary system. Although the brain/blood ratio increased significantly with time, the novel 99m Tc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.The γ-emitting 99m Tc is the most widely applied radionuclide in diagnostic imaging. Nevertheless, current research in radiopharmacology deals with the coordination chemistry of Tc as well as its congener Re with the aim to develop new radiotracers [1,2]. In the past decade, many efforts were focused on brainimaging Tc radiopharmaceuticals capable to cross the blood-brain barrier and localize in the brain. Although many of the Tc and Re complexes have been investigated to date, clear structural criteria involved in brain uptake and retention of technetium complexes are not fully documented.One of the important aspects in Tc radiotracer design is the complex lipophilicity [3]. Since distribution and passive transport through membranes are governed by lipophilicity, there is considerable interest in how lipophilicity parameters can be controlled by chemical modifications of the tracer molecule. This study on amine-bearing mixed-ligand Re complexes aims toward this goal. These studies are triggered by the fact that the amine-carrying Tc species are able to pass the intact blood-brain barrier and are accumulated in the brain [4,5]. Keeping in mind that Re complexes may serve as nonradioactive surrogates for their Tc analogs due to similar molecular properties, we studied Re(V) whose coordination core is stable enough to exist in aqueous solutions and versatile enough to combine with selected ligands. An example of such a core is the oxo form [Re V O] 3+ , in which the +5 oxidation state of the metal is stabilized by the oxo ligand [5,6]. The literature shows that a search for new radiopharmaceuticals requires studies of new oxorhenium(V) complexes with N-and S-donor ligands, as well as of their 99m Tc analogs. In this study we prepared and characterized a novel rhenium complex, [ReO(mer)(amino)OH· (H 2 O) 2 ]. We have also studied the radiochemical properties of the correspond...

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Section: Methodsmentioning

confidence: 99%

“…The organic solvent was expelled under a mild stream of nitrogen, and ethanol was added. A 30% ethanol final solution was obtained for the complex according to [16]. The radiolabeling yield was 88 ± 3% with ~96% radiochemical purity.…”

Section: Synthesis Of [Reo(mer)(amino)oh(h 2 O) 2 ]mentioning

confidence: 99%

Synthesis and characterization of a {ReO}3+ complex with S- and N-donor ligands and of its 99m Tc analog

Alhokbany

2012

Radiochemistry

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“…the in vivo distribution profile of the radiotracers according to literature [16]. The animal biodistribution experiments were performed in accordance with institutional, national and international regulations governing the safe and humane use of laboratory animals in research.…”

Section: Methodsmentioning

confidence: 99%

“…The radioactivity content of both the aqueous and organic phase is measured separately. The organic solvent was expelled under a mild stream of nitrogen, and ethanol was added so that a final solution 30% ethanol final solution was obtained for complex according to literature [16]. The radiolabeling yield was 88% ± 3% with 96% radiochemical purity.…”

Section: Synthesis Of [Reo(imz)(hyd)(h 2 O) 2 Oh]mentioning

confidence: 99%

“…TLC and HPLC analyses were used to evaluate the radiochemical purity (RCP) and the stability of the complex. ITLC was performed on instant thin layer chromatography with Whatman No.1 chromatography paper and using acetone and saline as the mobile phase according to literature [16]. Rf values for [ 99m TcO(Imz)(Hyd)OH] were around 0.6 in acetone; the other values are reported in Table 6.…”

Section: Geometry Optimization Charge Distribution Electronic Strucmentioning

confidence: 99%

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New oxorhenium (V) complex with an imidazol [NN] /hydantoin [SN] mixed ligand system, and radiochemical behavior of its oxotechnetium (V) complex analog

Alhokbany

Mahfouz²,

Al-Jammaz³

2011

JBPC

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A [ReO(Imz)(Hyd)(H 2 O) 2 OH] complex was successfully synthesized by the ligand exchange method using oxorhenuim citrate and an imidazole /Hydanton mixed ligand system. Geometry optimization of complex has been carried out using DFT at the B3LYP/LANL2DZ functional in singlet state. B3LYP predicated infrared spectrum of the geometrically optimized structure using the same level of the theory and the same base set showed good agreement with experimentally observed values. The spin allowed singlet-singlet electronic transition of the [ReO(Imz)(Hyd) (H 2 O) 2 OH] complex was calculated with time dependent density function theory (TD-DFT) and the UV-Vis spectra has been discussed on this basis. The complex was characterized using microanalysis and IR, UVVis, NMR and mass spectroscopic. The technetium tracer [ 99m TcO(Imz)(Hyd) (H 2 O) 2 OH] has also been synthesized by two methods using 99m Tc-gluconate as a precursor or; by direct reduction. The radiochemical purity of the complex was over 95% as measured by thin layer chromatography. In vitro studies showed that the complex possessed good stability under physiological conditions. The partition coefficient indicated that the complex hydrophilic and the electrophoresis results showed that the complex cationic. Biodistrbution in mice showed that the complex accumulated in heart uptake of 9.53 ± 3.87% ID/gm at 5 min and good retention (6.37 ± 1.21)% ID/gm at 60 min. One hour after the injection, the heart/liver, heart/lung and heart/blood radioactivity ratios were 0.46, 1.04 and 0.56, respectively. These findings indicate that the complex might be suitable for myocardial imaging.

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Synthesis and Characterization of Thiol Containing Furoxan Derivatives as Coligands for the Preparation of Potential Bioreductive Radiopharmaceuticals

Cerecetto

González

Onetto

et al. 2006

Archiv der Pharmazie

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The synthesis and characterization of thiol-containing 1,2,5-oxadiazole N-oxide (TONO) derivatives and their use as monodentate coligands for the preparation of (99m)Tc complexes is presented. 3-Mercaptomethyl-4-phenyl-1,2,5-oxadiazol N(2)-oxide and 3-(4-mercaptophenylmethylidenhydrazinocarbonyloxymethyl)-4-phenyl-1,2,5-oxadiazol N(2)-oxide were successfully synthesized and combined with the tridentate ligand N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA) to prepare "3+1 mixed ligand" technetium complexes. The( 99m)Tc complexes were obtained in high yield and radiochemical purity using low concentration of ligand and coligand. An alternative procedure using a xantate and a disulphide precursor of 3-mercaptomethyl-4-phenyl-1,2,5-oxadiazol N(2)-oxide yielded the same complex. Biological evaluation of the potentiality of the( 99m)Tc complexes as bioreductive radiopharmaceuticals was performed in normal CD1 mice and in mice bearing induced sarcoma. Tumour uptake was moderate but tumour/soft tissue ratio was favourable. Although these results are encouraging, further development is still necessary in order to achieve higher tumour uptake and lower gastrointestinal activity.

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Synthesis, characterization and biological evaluation of a novel “3 + 1” mixed ligand 99mTc complex having an aliphatic thiol as coligand

Cited by 7 publications

References 19 publications

Synthesis and characterization of a {ReO}3+ complex with S- and N-donor ligands and of its 99m Tc analog

Synthesis and characterization of a {ReO}3+ complex with S- and N-donor ligands and of its 99m Tc analog

New oxorhenium (V) complex with an imidazol [NN] /hydantoin [SN] mixed ligand system, and radiochemical behavior of its oxotechnetium (V) complex analog

Synthesis and Characterization of Thiol Containing Furoxan Derivatives as Coligands for the Preparation of Potential Bioreductive Radiopharmaceuticals

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