Sidi Bou Saïd, Tunisia
Sidi Bou Saïd, Tunisia

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Malek-Saied N.,Radiopharmaceutical Unit | Aissi R.E.,Radiopharmaceutical Unit | Aissi R.E.,French National Center for Scientific Research | Aissi R.E.,Toulouse 1 University Capitole | And 3 more authors.
Applied Organometallic Chemistry | Year: 2011

A new cytectrene prototype of general formula RCpTc(CO)3 (R = C6H5NHCO, Cp = cyclopentadienyl moiety) has been synthesized from N-phenylferrocenecarboxamide 2, characterized and evaluated as a potential brain perfusion imaging agent. An improved procedure has been developed to obtain both the ligand 2, characterized by its solid-state structure (orthorhombic, Pccn, a = 10.4443(2) Å, b = 26.1467(6) Å, c = 9.9977(3) Å), and the corresponding metallic Tc- and Re-complexes in good yield. These latter complexes possessed similar HPLC retention times, thereby indicating identity of their molecular structures. The Tc-complex 99mTc-2 is lipophilic enough to cross the blood-brain barrier. This complex exhibits good brain uptake (1.41% injected dose per gram tissue at 5 min) combined with a fairly good retention of radioactivity in brain (0.48% injected dose per gram tissue after 1 h). Then, the distribution of the activity at 5 min post-injection in various rat brain regions showed a higher accumulation in the hippocampus area. The new 99mTc- cyclopentadienyltricarbonyl technetium complex reported here showed promising biological results, making it an interesting base for the development of a new generation of cytectrene as brain perfusion imaging agent. Copyright © 2011 John Wiley & Sons, Ltd.


Saied N.M.,Radiopharmaceutical Unit | Mejri N.,Radiopharmaceutical Unit | El Aissi R.,Radiopharmaceutical Unit | El Aissi R.,French National Center for Scientific Research | And 4 more authors.
European Journal of Medicinal Chemistry | Year: 2015

The goal of this study is to develop a novel brain receptor imaging agent. This study reports the synthesis, characterization and the biological evaluation of 1-((2-methoxyphenyl) piperazine)ferrocenecarboxamide labeled with technetium-99 m (99mTc-MP). The 99mTc-MP was obtained quickly (radiolabelling time < 5 min), in 90% yield. The 99mTc-complex, characterized by HPLC (20-50% ACN of 0 at 5 min then 50% ACN of 5 at 17 min to finally with 50 at 20% ACN of 17 at 20 min), is stable, neutral and lipophilic enough to cross the blood-brain barrier which was confirmed by octanol/water partition coefficient (LogP = 1.82). In vivo biodistribution indicated that this complex had exceptional brain uptake (2.47% ID/g at 5 min and 0.75% ID/g at 60 min). The distribution of the activity at 15 min post-injection in various rat brain regions showed a higher accumulation in the hippocampus area. After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 0.87% ID/g to 0.21% ID/g at 15 min p.i., while the cerebellum had no significant decrease. The new 99mTc-cyclopentadienyltricarbonyl technetium complex reported here showed promising biological results, making it an interesting starting point for the development of a new 99mTc-complex as brain receptor imaging agent. © 2015 Elsevier Masson SAS.


PubMed | French National Center for Scientific Research and Radiopharmaceutical Unit
Type: | Journal: European journal of medicinal chemistry | Year: 2015

The goal of this study is to develop a novel brain receptor imaging agent. This study reports the synthesis, characterization and the biological evaluation of 1-((2-methoxyphenyl) piperazine)ferrocenecarboxamide labeled with technetium-99m ((99m)Tc-MP). The (99m)Tc-MP was obtained quickly (radiolabelling time<5min), in 90% yield. The (99m)Tc-complex, characterized by HPLC (20-50% ACN of 0at 5min then 50% ACN of 5 at 17min to finally with 50 at 20% ACN of 17 at 20min), is stable, neutral and lipophilic enough to cross the blood-brain barrier which was confirmed by octanol/water partition coefficient (LogP=1.82). Invivo biodistribution indicated that this complex had exceptional brain uptake (2.47% ID/g at 5min and 0.75% ID/g at 60min). The distribution of the activity at 15minpost-injection in various rat brain regions showed a higher accumulation in the hippocampus area. After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 0.87% ID/g to 0.21% ID/g at 15min p.i., while the cerebellum had no significant decrease. The new (99m)Tc-cyclopentadienyltricarbonyl technetium complex reported here showed promising biological results, making it an interesting starting point for the development of a new (99m)Tc-complex as brain receptor imaging agent.


Guizani S.,Radiopharmaceutical Unit | Malek Saied N.,Radiopharmaceutical Unit | Picard C.,CNRS Chemistry Laboratory | Picard C.,Toulouse 1 University Capitole | And 3 more authors.
Journal of Labelled Compounds and Radiopharmaceuticals | Year: 2014

A novel bifunctional chelating agent based on a click chemistry strategy has been synthesized and characterized on the basis of spectroscopic techniques. The metal chelating part of this new class of tridentate N2O ligand combined a triazole unit and an aromatic ring. This latter semi-rigid framework induced a pre-organization of the chelating cavity, improving the stability of the corresponding metallic complexes (M = 99mTc, Re). Thus, the 99mTc(CO)3 complex, obtained with good yield and excellent radiochemical purity (>90%), exhibited a high in vitro serum stability. Tissue biodistribution in normal mice showed a rapid clearance, no long-term retention in organs and no in vivo reoxidation of technetium-99m, making this compound a promising 99mTc-chelating system. Copyright © 2014 John Wiley & Sons, Ltd.


Essouissi I.,Radiopharmaceutical Unit | Saied N.M.,Radiopharmaceutical Unit | Mejri N.,Radiopharmaceutical Unit | Guizani S.,Radiopharmaceutical Unit | And 2 more authors.
Journal of Radioanalytical and Nuclear Chemistry | Year: 2014

In this work we propose a technetium-99m-labeled derivative from Ethionamide (ETH), further referred to as 99mTc-ECF for tuberculosis diagnosis. The biological features of this radioactive agent have been studied. The 2-ethylpyridine-4-carbothioamide-ferrocène (ECF) was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that 99mTc-ECF is obtained with high radiolabelling yield (>90 %). Radiochemical analysis of 99mTc-ECF revealed that the molecule was efficiently labeled with a little free remaining pertechnetate. Only 1-2 % of the tracer was leached out from the complex at 24 h when incubated in serum at 37°C which confirmed its high stability. The sensitivity test of ECF showed that the group of grafted ferrocenyl does not seem to have largely altered the active site of the molecule. In-vitro investigations were conducted using BCG (Bacille Calmette-Guérin) as analogue of Mycobacterium Tuberculosis and Listeria Monocytogenes as negative control. It was proved that for BCG, ECF has kept the bacteriostatic properties of the parent compound (ETH). In physiological conditions, the measured up-take of the tracer with live bacteria was about 24.1 and 7.1 % for BCG and Listeria Monocytogenese, respectively. The comparison of the 99mTc-ECF accumulation at sites of BCG infected animals, which is expressed as target-to-non-target ratio (found to be equal to 2.15) with other radiotracers was discussed. This allowed us to consider that 99mTc-ECF could be a reasonable radiotracer for mycobacterial infections. Obtained results were good and encourage to undergo a similar labeling for the Mycobacterium tuberculosis as perspective of this work. © 2014 Akadémiai Kiadó.


Essouissi I.,Ibn Al Baytar Society of Pharmaceutical Industries | Essouissi I.,Radiopharmaceutical Unit | Darghoutha F.,Ibn Al Baytar Society of Pharmaceutical Industries | Saied N.M.,Radiopharmaceutical Unit | And 3 more authors.
Radiochemistry | Year: 2015

Sulfadiazine (antibiotic used for treating bacterial infections) was labeled with 99mTc with the aim of the development of a new radiopharmaceutical for infection imaging. The influence of the reaction parameters such as the substrate and SnCl2·2H2O concentrations, pH of the reaction mixture, and reaction time on the labeling yield was examined, and the labeling conditions were optimized. The maximum radiochemical yield of 99mTc-sulfadiazine (94.7%) was obtained by using 50 μg of SnCl2·2H2O and 1 mg of sulfadiazine at pH 5. The radiochemical purity of the labeled compound was evaluated by ITLC and HPLC. The biological distribution of 99mTc-sulfadiazine in mice with experimentally induced Staphylococcus aureus infection in the right thigh was studied, and the bacterial infected thigh/normal thigh (target-to-nontarget, T/NT) ratio was evaluated. The T/NT ratio for 99mTc-sulfadiazine was found to be 3.6, which is comparable to the commercially available 99mTc-ciprofloxacin (3.8), indicating that 99mTc-sulfadiazine can be used for infection imaging. © 2015 Pleiades Publishing, Inc.


Mejri N.,Radiopharmaceutical Unit | Barhoumi C.,Radiopharmaceutical Unit | Trabelsi M.,Radiopharmaceutical Unit | Mekni A.,Radiopharmaceutical Unit | And 2 more authors.
Nuclear Medicine and Biology | Year: 2010

Alzheimer's disease (AD) is a degenerative neurological disorder that causes progressive and irreversible loss of connections between brain cells and loss of mental functions. Clinical and postmortem studies show that the biochemical changes in brains of AD patients include decrease in acetylcholinesterase (AChE) activity. Our aim was to study AChE activity using piperidinyl ester labelled with technetium-99m. In vivo and in vitro studies demonstrated that labelled piperidinyl ester was a substrate for AChE. The hydrolytic rate of this substrate was measured and the specificity was evaluated using the inhibitor BW284c51. The rhenium analogues of the technetium-labelled substrate were used to determine the affinity constant (Km) and the maximum reaction velocity (Vmax) because of the high specific activity of technetium. The high hydrolytic rate and high specificity of the substrate for AChE make it suitable as an in vivo radiotracer for studying AChE activity in the brain. © 2010 Elsevier Inc. All rights reserved.


Essouissi I.,Radiopharmaceutical Unit | Ghali W.,Radiopharmaceutical Unit | Saied N.M.,Radiopharmaceutical Unit | Saidi M.,Radiopharmaceutical Unit
Nuclear Medicine and Biology | Year: 2010

A technetium-99m-labeled derivative from sulfanilamide, further referred to as 99mTc-N-SFC, targeting infections in experimental animals, has been synthesized. The biological features of this radioactive agent have also been studied. The N-sulfanilamide ferrocene carboxamide (N-SFC) was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that it is stable and obtained with radiolabelling yield (>87%). Radiochemical analyses of 99mTc-N-SFC revealed that the molecule was labeled rapidly (within 2 min) and effectively with little free pertechnetate in the preparations containing purified compound. Furthermore, in vitro investigations were conducted and the label's stability in serum was observed up to 24 h of testing. Uptake of the tracer with live and heat/killed bacteria was compared in physiological conditions and was about 69% and 61.9% for the Escherichia coli and Staphylococcus aureus strains, respectively. We concluded that synthesis and labeling of Sulfanilamide derivative with 99m-Tc by this method is rapid, efficient and safe. Biodistribution studies demonstrated that our radiolabeled compound is accumulated rapidly and significantly (P<.05) at infection sites. The comparison of the 99mTc-N-SFC accumulation at sites of S. aureus-infected animals, which is expressed as target-to-non-target ratio, (2.88±0.10) with other radiotracers was discussed. © 2010 Elsevier Inc.


PubMed | Radiopharmaceutical Unit
Type: Journal Article | Journal: Nuclear medicine and biology | Year: 2010

A technetium-99m-labeled derivative from sulfanilamide, further referred to as (99m)Tc-N-SFC, targeting infections in experimental animals, has been synthesized. The biological features of this radioactive agent have also been studied. The N-sulfanilamide ferrocene carboxamide (N-SFC) was chemically synthesized and then labeled with technetium-99m. It has been confirmed through this work that it is stable and obtained with radiolabelling yield (>87%). Radiochemical analyses of (99m)Tc-N-SFC revealed that the molecule was labeled rapidly (within 2 min) and effectively with little free pertechnetate in the preparations containing purified compound. Furthermore, in vitro investigations were conducted and the labels stability in serum was observed up to 24 h of testing. Uptake of the tracer with live and heat/killed bacteria was compared in physiological conditions and was about 69% and 61.9% for the Escherichia coli and Staphylococcus aureus strains, respectively. We concluded that synthesis and labeling of Sulfanilamide derivative with (99m-)Tc by this method is rapid, efficient and safe. Biodistribution studies demonstrated that our radiolabeled compound is accumulated rapidly and significantly (P<.05) at infection sites. The comparison of the (99m)Tc-N-SFC accumulation at sites of S. aureus-infected animals, which is expressed as target-to-non-target ratio, (2.88 0.10) with other radiotracers was discussed.


PubMed | Radiopharmaceutical Unit
Type: Journal Article | Journal: Nuclear medicine and biology | Year: 2010

Alzheimers disease (AD) is a degenerative neurological disorder that causes progressive and irreversible loss of connections between brain cells and loss of mental functions. Clinical and postmortem studies show that the biochemical changes in brains of AD patients include decrease in acetylcholinesterase (AChE) activity. Our aim was to study AChE activity using piperidinyl ester labelled with technetium-99m. In vivo and in vitro studies demonstrated that labelled piperidinyl ester was a substrate for AChE. The hydrolytic rate of this substrate was measured and the specificity was evaluated using the inhibitor BW284c51. The rhenium analogues of the technetium-labelled substrate were used to determine the affinity constant (K(m)) and the maximum reaction velocity (V(max)) because of the high specific activity of technetium. The high hydrolytic rate and high specificity of the substrate for AChE make it suitable as an in vivo radiotracer for studying AChE activity in the brain.

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