Radiopharmaceutical Unit

Sidi Bou Saïd, Tunisia

Radiopharmaceutical Unit

Sidi Bou Saïd, Tunisia
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Mejri N.,University of Bern | Mejri N.,Radiopharmaceutical Unit | Muller J.,University of Bern | Gottstein B.,University of Bern
Parasite Immunology | Year: 2011

Intraperitoneal larval infection (alveolar echinococcosis, AE) with Echinococcus multilocularis in mice impairs host immunity. Metacestode metabolites may modulate immunity putatively via dendritic cells. During murine AE, a relative increase of peritoneal DCs (pe-DCs) in infected mice (AE-pe-DCs; 4% of total peritoneal cells) as compared to control mice (naïve pe-DCs; 2%) became apparent in our study. The differentiation of AE-pe-DCs into TGF-β-expressing cells and the higher level of IL-4 than IFN-γ/IL-2 mRNA expression in AE-CD4+pe-T cells indicated a Th2 orientation. Analysis of major accessory molecule expression on pe-DCs from AE-infected mice revealed that CD80 and CD86 were down-regulated on AE-pe-DCs, while ICAM-1(CD54) remained practically unchanged. Moreover, AE-pe-DCs had a weaker surface expression of MHC class II (Ia) molecules as compared to naïve pe-DCs. The gene expression level of molecules involved in MHC class II (Ia) synthesis and formation of MHC class II (Ia)-peptide complexes were down-regulated. In addition, metacestodes excreted/secreted (E/S) or vesicle-fluid (V/F) antigens were found to alter MHC class II molecule expression on the surface of BMDCs. Finally, conversely to naïve pe-DCs, an increasing number of AE-pe-DCs down-regulated Con A-induced proliferation of naïve CD4+pe-T cells. These findings altogether suggested that TGF-β-expressing immature AE-pe-DCs might play a significant role in the generation of a regulatory immune response within the peritoneal cavity of AE-infected mice. © 2011 Blackwell Publishing Ltd.


Mejri N.,Radiopharmaceutical Unit
Iranian journal of immunology : IJI | Year: 2017

BACKGROUND: Despite advances toward an improved understanding of the evasive mechanisms leading to the establishment of cystic echinococcosis, the discovery of specific immunosuppressive mechanisms and related factors are of great interest in the development of an immunotherapeutic approach.OBJECTIVE: To elucidate immunosuppressive effects of bioactive factors contained in chromatographic fractions from hydatid cystic fluid (HCF) of Echinococcus granulosus.METHODS: Hydatid cystic fluid was fractionated by reverse phase chromatography. Non-specific Concanavalin A-driven proliferation of spleen cells was used to determine specific inhibitory fractions. Trypan blue exclusion test and flowcytometry analysis were performed to check whether highly inhibitory fractions of HCF have apoptotic effect on peritoneal macrophages. Western blot analysis was used to determine proteolytic effects of parasitic antigens on major histocompatibility complex (MHC) class II (I-a) contained in membrane proteins extract from macrophages.RESULTS: High concentrations of HCF and few of chromatographic fractions suppressed spleen cells proliferation. Fractions 7 and 35 were the highest inhibitory fractions. Specifically fraction 35 and to a lesser extent HCF induced apoptosis in peritoneal naive macrophages. However, HCF and the fraction 7 proteolytically altered the expression of MHC class II molecules on peritoneal macrophages. The proteolytic molecule was identified to be a serine protease. Macrophages taken at the chronic and end phase from cystic echinococcosis-infected mice were able to uptake and process C-Ovalbumine-FITC. These cells expressed a drastically reduced level of (I-a) molecules.CONCLUSION: Our study present new aspects of immune suppression function of E. granulosus. Further molecular characterization of apoptotic and proteolytic factors might be useful to develop immunotherapeutic procedure to break down their inhibitory effects.


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.


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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