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M Papadopoulos

Publications and source records attributed to M Papadopoulos.

At least 19 recordsLinked to original sources
PubMed2006

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

The synthesis and evaluation of a series of oxotechnetium and oxorhenium complexes containing a nitroaromatic moiety as potential radiopharmaceuticals for targeting tumour hypoxia is presented. 99mTc labelling was performed in high yield (>85%) and radiochemical purity (>90%). Their structure was corroborated by means of the rhenium complexes. Reduction potentials were in the range for bioreducible compounds. 99mTc complexes III-VI were selected for "in vivo" experiments in view of the results of cytotoxicity studies. Biodistribution in normal animals was characterized by high initial blood, lung and liver uptake, fast blood and soft tissue depuration and preferential excretion via the hepatobiliary system. Initial tumour uptake was moderate but tumour/muscle ratios for complexes III and IV, were favourable at all time points. Although the results are encouraging further development is still necessary in order to achieve higher tumour uptake and lower gastrointestinal activity.

Animals↗
PubMed2005

(S)-(2-(2'-Pyridyl)ethyl)cysteamine and (S)-(2-(2'-pyridyl)ethyl)-d,l-homocysteine as ligands for the "fac-[M(CO)(3)](+)" (M = Re, (99m)Tc) core.

The reaction of fac-[NEt(4)](2)[Re(CO)(3)Br(3)] with (S)-(2-(2'-pyridyl)ethyl)cysteamine, L(1), in methanol leads to the formation of the cationic fac-[Re(CO)(3)(NSN)][Br] complex, 1, with coordination of the nitrogen of the pyridine, the sulfur of the thioether, and the nitrogen of the primary amine. When fac-[NEt(4)](2)[Re(CO)(3)Br(3)] reacts with the homocysteine derivative (S)-(2-(2'-pyridyl)ethyl)-d,l-homocysteine, L(2), the neutral fac-Re(CO)(3)(NSO) complex, 2, is produced with coordination of the nitrogen of the primary amine, the sulfur of the thioether, and the oxygen of the carboxylate group, while the pyridine ring remains uncoordinated. The analogous technetium-99m complexes, 1' and 2', were also prepared quantitatively by the reaction of L(1) and L(2) with the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor at 70 degrees C in water. Given that both (S)-(2-(2'-pyridyl)ethyl)cysteamine and homocysteine can be easily N- or S-derivatized by a bioactive molecule of interest, both the NSN or NSO ligand systems could be used to develop target-specific radiopharmaceuticals for diagnosis and therapy.

Crystallography, X-Ray↗
PubMed2002

Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.

The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

Animals↗
PubMed2002

Oxotechnetium 99mTcO[SN(R)S][S] complexes as potential 5-HT1A receptor imaging agents.

A series of 99mTcO[SN(R)S][S] complexes carrying the 1-(2-methoxyphenyl)piperazine moiety on the tridentate ligand [SN(R)S] was synthesized. For structural characterization and for in vitro binding assays the analogous oxorhenium complexes were prepared. As demonstrated by appropriate competition binding tests in rat hippocampal preparations, all oxorhenium analogues showed affinity for the 5-HT(1A) receptor binding sites with IC(50) values at the nanomolar range (IC(50)= 5.8-103 nM). All 99mTcO[SN(R)S]/[S] complexes showed significant brain uptake in rats at 2 min p.i. (0.24-1.31% ID). However, a clear correlation between distribution of radioactivity in the brain and distribution of 5-HT(1A) receptors could not be established.

Animals↗
PubMed2001

Novel oxorhenium and oxotechnetium complexes from an aminothiol[NS]/thiol[S] mixed-ligand system.

The simultaneous action of a bidentate aminothiol ligand, LnH, (n = 1: (CH3CH2)2NCH2CH2SH and n = 2: C5H10NCH2CH2SH) and a monodentate thiol ligand, LH (LH: p-methoxythiophenol) on a suitable MO (M = Re, 99gTc) precursor results in the formation of complexes of the general formula [MO(Ln)(L)3] (1, 2 for Re and 5. 6 for 99gTc). In solution these complexes gradually transform to [MO(Ln)(L)2] complexes (3, 4 for Re and 7, 8 for 99gTc). The transformation is much faster for oxotechnetium than for oxorhenium complexes. Complexes 1-4, 7, and 8 have been isolated and fully characterized by elemental analysis and spectroscopic methods. Detailed NMR assignments were made for complexes 3, 4, 7, and 8. X-ray studies have demonstrated that the coordination geometry around rhenium in complex 1 is square pyramidal (tau = 0.06), with four sulfur atoms (one from the L1H ligand and three from three molecules of p-methoxythiophenol) in the basal plane and the oxo group in the apical position. The L1H ligand acts as a monodentate ligand with the nitrogen atom being protonated and hydrogen bonded to the oxo group. The four thiols are deprotonated during complexation resulting in a complex with an overall charge of zero. The coordination geometry around rhenium in complex 4 is trigonally distorted square pyramidal (tau = 0.41), while in the oxotechnetium complex 7 it is square pyramidal (tau = 0.16). In both complexes LnH acts as a bidentate ligand. The NS donor atom set of the bidentate ligand and the two sulfur atoms of the two monodentate thiols define the basal plane, while the oxygen atom occupies the apical position. At the technetium tracer level (99mTc), both types of complexes, [99mTcO(Ln)(L)3] and [99mTcO(Ln)(L)2], are formed as indicated by HPLC. At high ligand concentrations the major complex is [99mTcO(Ln)(L)3], while at low concentrations the predominant complex is [99mTcO(Ln)(L)2]. The complexes [99mTcO(Ln)(L)3] transform to the stable complexes [99mTcO(Ln)(L)2]. This transformation is much faster in the absence of ligands. The complexes [99mTcO(Ln)(L)2] are stable, neutral, and also the predominant product of the reaction when low concentrations of ligands are used, a fact that is very important from the radiopharmaceutical point of view.

Amines↗
PubMed2001

Novel lipophilic amidate oxorhenium and oxotechnetium complexes as potential brain agents: synthesis, characterization and biological evaluation.

Novel oxorhenium and oxotechnetium complexes based on the tetradentate 1-(2-hydroxybenzamido)-2-(pyridinecarboxamido)benzene, H3L, ligand have been synthesized and characterized herein. Thus, by reacting equimolar quantities of the triply deprotonated ligand L3- with the suitable MO3+ precursor, the following neutral MOL complexes could be easily produced following similar synthetic routes: M = Re (1), M = 99gTc (2), and M = 99mTc (3). Complexes 1 and 2, prepared in macroscopic amounts, were chemically characterized and their structure determined by single-crystal X-ray analysis. They are isostructural metal chelates, adopting a distorted square pyramidal geometry around the metal. The N3O donor atom set of the tetradentate ligand defines the basal plane and the oxygen atom of the M = O core occupies the apex of the pyramid. Complex 3 forms quantitatively at tracer level by mixing the H3L ligand with Na99mTcO4 generator eluate in aqueous alkaline media and using tin chloride as reductant in the presence of citrate. Its structure was established by chromatographic comparison with prototypic complexes 1 and 2 using high-performance liquid chromatographic techniques. When challenged with excess glutathione in vitro, complex 3 is rapidly converted to hydrophilic unidentified metal species. Tissue distribution data after administration of complex 3 in vivo revealed a significant uptake and retention of this compound in brain tissue.

Animals↗
PubMed2001

Development of novel mixed-ligand oxotechnetium [SNS/S] complexes as potential 5-HT1A receptor imaging agents.

The "3 + 1" ligand system [SN(R)S/S combination] was applied in order to synthesize neutral mixed-ligand oxotechnetium complexes of the general formula 99mTcO[SN(R)S]/[S] as potential 5-HT1A receptor imaging agents. The complexes are carrying the 1-(2-methoxyphenyl)piperazine moiety, a fragment of the true 5-HT1A antagonist WAY 100635, either on the monodentate ligand [S] or on the tridentate ligand [SN(R)S]. The complexes MO[EtN(CH2CH2S)2] [o-MeOC6H4N(CH2CH2)2NCH2CH2S] (3), MO[o- MeOC6H4N(CH2CH2)2N(CH2)3N(CH2CH2S)2][PhS] (6) and MO[o-MeOC6H4N(CH2CH2)2N(CH2)3N(CH2CH2S)2] [PhCH2CH2S] (9), where M = 99mTc, were prepared at tracer level using 99mTc glucoheptonate as precursor. For structural characterization, the analogous oxorhenium (M = Re, 1, 4 and 7, respectively) and oxotechnetium (M = 99gTc, 2, 5 and 8, respectively) complexes were prepared by ligand exchange reactions. All products were characterized by elemental analysis and spectroscopic methods. Complexes 1, 4 and 7 were further characterized by crystallographic analysis. For 1, the coordination geometry about rhenium can be described as trigonally distorted square pyramidal (tau = 0.36), while for 4 and 7, as distorted trigonal bipyramidal (tau = 0.66 and tau = 0.61, respectively). The coordination sphere about oxorhenium in all complexes is defined by the SNS donor atom set of the tridentate ligand and the sulfur atom of the monodentate coligand. The structure of the 99mTc complexes 3, 6 and 9 was established by comparative HPLC using authentic oxorhenium and oxotechnetium samples. The binding affinity of oxorhenium compounds for the 5-HT1A receptor subtype was determined in rat brain hippocampal preparations (IC50 = 6-31 nM). Preliminary tissue distribution data in healthy mice revealed the ability of all three 99mTc complexes to cross the intact blood-brain barrier (0.49-1.15% ID at 1 min p.i.). In addition, complexes 6 and 9 showed significant brain retention. These promising results have demonstrated that the SNS/S mixed-ligand system can be used in the development of 99mTc complexes as potential 5-HT1A receptor imaging agents.

Animals↗
PubMed2001

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

A novel "3 + 1" mixed ligand 99mTc complex with N,N-bis(2-mercaptoethyl)-N'N'-diethyl-ethilenediamine as ligand and 1-octanethiol as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using 99mTc-glucoheptonate as precursor and a coligand/ligand ratio of 5. Under these conditions the labeling yield was over 80% and a major product with radiochemical purity >80% was isolated by HPLC methods and used for biological evaluation. Chemical characterization at carrier level was developed using the corresponding rhenium and 99gTc complexes. Results were consistent with the expected "3 + 1" structure and X-ray diffraction study demonstrated that the complex adopted a distorted trigonal bipyramidal geometry. All sulphur atoms underwent ionization leading to the formation of a neutral compound. Biodistribution in mice demonstrated early brain uptake, fast blood clearance and excretion through hepatobiliary system. Although brain/blood ratio increased significantly with time, this novel 99mTc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.

Animals↗
PubMed2001

Ester-modified 99mTcO[SN(R)S/S] mixed ligand complexes: synthesis and preliminary evaluation.

Two novel 99mTc-(SNS/S) complexes: a mono-ester compound carrying an ethyl ester group on the tridentate ligand, 99mTcO[C(2)H(5)OOCCH(2)N(CH(2)CH(2)S)(2)][SC(6)H(4)CH(3)], 3, and a diester compound, carrying a second ethyl ester group on the monodentate ligand, 99mTcO[C(2)H(5)OOCCH(2)N(CH(2)CH(2)S)(2)][SC(6)H(4)COOC(2)H(5)], 4, were synthesized. The corresponding oxorhenium(V) complexes, 1 and 2 were also synthesized. Enzymatic hydrolysis demonstrated that 3 remains intact after 10 min incubation while 4 is totally converted to an unidentified hydrophilic complex. Tissue distribution data in mice revealed that both complexes, 3 and 4, exhibit significant initial brain uptake (1.42 and 1.01% of injected dose at 5 minutes post injection respectively) and fast blood clearance.

Animals↗
PubMed2000

Synthesis and characterization of mixed-ligand oxorhenium complexes with the SNN type of ligand. Isolation of a novel ReO[SN][S][S] complex.

A new series of mixed-ligand oxorhenium complexes 4-9, with ligands 1-3 (L1H2) containing the SNN donor set and monodentate thiols as coligands (L2H), is reported. All complexes were synthesized using ReOCl3(PPh3)2 as precursor. They were isolated as crystalline products and characterized by elemental analysis and IR and NMR spectroscopy. The ligands 1 and 2 (general formula RCH2CH2NHCH2CH2SH, where R = N(C2H5)2 in 1 and pyrrolidin-1-yl in 2) act as tridentate SNN chelates to the ReO3+ core, leaving one open coordination site cis to the oxo group. The fourth coordination site is occupied by a monodentate aromatic thiol which acts as a coligand. Thus, three new "3 + 1" [SNN][S] oxorhenium complexes 4-6 (general formula ReO[RCH2CH2NCH2CH2S][SX], where R = N(C2H5)2 and X = phenyl in 4, R = N(C2H5)2 and X = p-methylphenyl in 5, and R = pyrrolidinlyl and X = p-methylphenyl in 6) were prepared in high yield. Complex 4 adopts an almost perfect square pyramidal geometry (tau = 0.07), while 6 forms a distorted square pyramidal geometry (tau = 0.24). In both complexes 4 and 6, the basal plane is formed by the SNN donor set of the tridentate ligand and the S of the monodentate thiol. On the other hand, the ligand 3, [(CH3)2CH]2NCH2CH2NHCH2CH2SH, acts as a bidentate ligand, probably due to steric hindrance, and it coordinates to the ReO3+ core through the SN atoms, leaving two open coordination sites cis to the oxo group. These two vacant positions are occupied by two molecules of the monodentate thiol coligand, producing a novel type of "2 + 1 + 1" [SN][S][S] oxorhenium mixed-ligand complexes 7-9 (general formula ReO[[(CH3)2CH]2NCH2CH2NHCH2CH2S][SX][SX], where X = phenyl in 7, p-methylphenyl in 8, and benzyl in 9). The coordination sphere about rhenium in 7 and 8 consists of the SN donor set of ligand 3, two sulfurs of the two monodentate thiols, and the doubly bonded oxygen atom in a trigonally distorted square pyramidal geometry (tau = 0.44 and 0.45 for 7 and 8, respectively). Detailed NMR assignments were determined for complexes 5 and 8.

Journal Article↗
PubMed2000

Synthesis and characterization of six-coordinate "3 + 2" mixed-ligand oxorhenium complexes with the o-diphenylphosphinophenolato ligand and tridentate coligands of different N and S donor atom combinations.

A series of octahedral six-coordinate oxorhenium(V) mixed ligand complexes containing the common [ReO(L)]2+ fragment (L = o-OC6H4P(C6H5)2] have been synthesized and characterized. Hence, it was shown that the [ReO(L)]2+ moiety can accommodate a variety of tridentate ligands containing a central amine group amenable to deprotonation and different combinations of lateral groups, such as ethylamine, substituted ethylamine, ethylthiol, and ethylthioether arms. In particular, by reaction of equimolar amounts of the pertinent HLn ligands with the [(n-C4H9)4N][ReOCl3(L)] precursor in refluxing acetonitrile/methanol or dichloromethane/methanol mixtures, the following series of [ReO(Ln)(L)]+/0 oxorhenium(V) complexes has been generated: ReO[[N(CH2CH2NH2)2][o-OC6H4P(C6H5)2]]Cl (1); ReO[[C2H5)2NCH2CH2NCH2CH2S][o-OC6H4P5)2]] (2); ReO[[(CH2)4NCH2CH2NCH2CH2S][o-OC6H4P(C6H4P(C6H5)2]] (3); and ReO[[C2H5SCH2CH2NCH2CH2S][o-OC6H4P(C6H5)2]] (4). The complexes are closed-shell 18-electron oxorhenium species, which adopt octahedral geometries both in solution and in the solid state, as established by conventional physicochemical techniques including multinuclear NMR and single-crystal X-ray diffraction analyses.

Journal Article↗
PubMed1998

Pyogenic granuloma of the cornea.

BACKGROUND: Ocular pyogenic granulomata are uncommon and are often associated with a chalazion or previous ocular and adnexal surgery The avascular nature of the cornea may explain the rarity of pyogenic granulomata at this site. We report on a case of corneal pyogenic granuloma following previous corneal surgery. METHODS: Ophthalmologists who had treated the patient previously were contacted and earlier clinical notes and histopathological examinations were reviewed. The clinical course following excision of the pyogenic granuloma is described, as are the histopathological findings. RESULTS: Histological examination confirmed the diagnosis of pyogenic granuloma. Excision was followed by a clinical recurrence at a different site with spontaneous resolution. CONCLUSIONS: Pyogenic granulomata of the cornea are rare. However, the present case illustrates the importance of considering benign inflammatory causes in the differential diagnosis of a corneal mass lesion so as to avoid unnecessarily aggressive intervention. To our knowledge, spontaneous resolution of a corneal pyogenic granuloma has not been previously described.

Aged↗
PubMed1997

Familial spongiform encephalopathy associated with a novel prion protein gene mutation.

Human prion diseases include Creutzfeldt-Jakob disease, Gerstmann-Stráussler-Scheinker disease, fatal familial insomnia, and kuru. Each of these diseases has a specific clinical presentation while spongiform encephalopathy, neuronal loss, and gliosis are their neuropathological hallmarks. We studied a Brazilian family with an autosomal dominant form of dementia. Nine members of the family were affected by a dementia with frontotemporal clinical features, with a mean age at onset of 44.8 +/- 3.8 years and a mean duration of symptoms of 4.2 +/- 2.4 years. Neuropathological examination of 3 patients showed severe spongiform change and neuronal loss in the deep cortical layers and in the putamen, but minimal gliosis in the most severely affected areas. The putamen and cerebellum, but not other areas of the affected brain, displayed prion protein immunoreactivity. A novel prion protein gene mutation causing a nonconservative substitution at codon 183 was identified in 2 neuropathologically confirmed affected individuals (mother and son). The mutation was transmitted in a mendelian fashion to 12 members of the family. Therefore, we identified a novel prion disease variant characterized by an early onset and long duration of the symptoms, severe spongiform change with minimal gliosis, associated with a prion protein gene mutation at codon 183.

Adult↗