Design and evaluation of “3 + 1” mixed ligand oxorhenium and oxotechnetium complexes bearing a nitroaromatic group with potential application in nuclear medicine oncology

Giglio, Javier; A, Rey; Cerecetto, Hugo; Pirmettis, Ioannis; Papadopoulos, Minas; León, Elsa; Monge, Antonio; Ceráin, Adela López de; Azqueta, Amaya; González, Mercedes; Fernández, Marcelo; Paolino, Andrea; León, A.

doi:10.1016/j.ejmech.2006.05.006

Cited by 26 publications

(10 citation statements)

References 30 publications

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“…The results obtained, were expressed as log P O/W and the data were represented as the mean ± the standard deviation is -0.142 ± 0.052. As expected, the compound has low lipophilicity [21] (Figures 9 and 10).…”

Section: Qualitymentioning

confidence: 80%

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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Section: Qualitymentioning

confidence: 80%

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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“…The excretion was preferentially via the hepatobiliary system. Giglio et al's results suggested that further development of nitrobenzene derivatives as tumor hypoxia marker was still needed to achieve higher tumor uptake and lower gastrointestinal activity [43].…”

Section: Metronidazolesmentioning

confidence: 99%

Recent Advances on Radionuclide Labeled Hypoxia-Imaging Agents

Li¹,

Chu

2012

CPD

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Hypoxic tissue exists in most of the solid tumors and hypoxia is a common character of these tumors. The existence of hypoxic tissue in the tumor decreases the efficacy of radiotherapy and chemotherapy. Radiolabeled hypoxia markers have been developed to measure the hypoxic tissue together with non-invasive imaging techniques such as PET, SPECT, and PET/CT. This offers a convenient approach to delineate the tumor providing useful information for diagnosing cancer and guiding the treatment plan. Bioreducible or-ganic compounds have been developed as the hypoxia markers to probe tissue hypoxia noninvasively because they can be reduced and metabolized under hypoxic conditions; form adducts with cell components, and thus be trapped in the hypoxic tissue. These compounds include nitroimidazoles and other redox-sensitive compounds such as BnAO and ATSM. Different radionuclides have been used to label these compounds such as technetium-99m, iodine-123, fluorine-18, copper-64, etc. In addition, to detect hypoxia with endogenous hypoxia markers such as carbonic anhydrase IX (CA IX) and hypoxia-inducible factor-1 (HIF-1), some radiolabeled tracers have also been developed. This article is an overview of the progress in this area in the past decade including the development of radiolabeled compounds for hypoxia detection and problems associated with the hypoxia marker development.

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“…The RCP was still over 97% after 5 h. The results (see below) show that the complex is stable in saline and plasma for at least 5 h, which is an important parameter to pursue biological studies. The lipophilicity of the compound was evaluated by determination of the distribution ratio (P) in the n-octanol-saline system: logP O/W = -0.153 ± 0.07, i.e., the lipophilicity, as expected [23], is low. For 99m TcO[SN] complexes with the benzene ring attached to the mercapto ring, the logP could be expected to be above 1.5 [24], but the amino group apparently makes the complex more hydrophilic.…”

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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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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Design and evaluation of “3 + 1” mixed ligand oxorhenium and oxotechnetium complexes bearing a nitroaromatic group with potential application in nuclear medicine oncology

Cited by 26 publications

References 30 publications

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

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

Recent Advances on Radionuclide Labeled Hypoxia-Imaging Agents

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

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