PubMed Health⌕ Search

Biomedical subjects

M S Papadopoulos

Publications and source records attributed to M S Papadopoulos.

7 recordsLinked to original sources
PubMed1999

Glutathione-mediated metabolism of technetium-99m SNS/S mixed ligand complexes: a proposed mechanism of brain retention.

Two series of [99mTc](SNS/S) mixed ligand complexes each carrying the N-diethylaminoethyl or the N-ethyl-substituted bis(2-mercaptoethyl)amine ligand (SNS) are produced at tracer level using tin chloride as reductant and glucoheptonate as transfer ligand. The identity of [99mTc](SNS/S) complexes is established by high-performance liquid chromatographic (HPLC) comparison with authentic rhenium samples. The para substituent R on the phenylthiolate coligand (S) ranges from electron-donating (-NH2) to electron-withdrawing (-NO2) groups, to study complex stability against nucleophiles as a result of N- and R-substitution. The relative resistance of [99mTc](SNS/S) complexes against nucleophilic attack of glutathione (GSH), a native nucleophilic thiol of 2 mM intracerebral concentration, is investigated in vitro by HPLC. The reaction of [99mTc](SNS/S) complexes with GSH is reversible and advances via substitution of the monothiolate ligand by GS- and concomitant formation of the hydrophilic [99mTc](SNS/GS) daughter compound. The N-diethylaminoethyl complexes are found to be more reactive against GSH as compared to the N-ethyl ones. Complex reactivity as a result of R-substitution follows the sequence -NO2 >> -H > -NH2. These in vitro findings correlate well with in vivo distribution data in mice. Thus, brain retention parallels complex susceptibility to GSH attack. Furthermore, isolation of the hydrophilic [99mTc](SNS/GS) metabolite from biological fluids and brain homogenates provides additional evidence that the brain retention mechanism of [99mTc](SNS/S) complexes is GSH-mediated.

Animals↗
PubMed1999

Characterization and preliminary evaluation of ester-modified technetium-99m SNS/S mixed ligand complexes as potential brain perfusion agents.

Two novel [99mTc](SNS/S) mixed ligand complexes carrying a pendant ester function on the monothiolate coligand were synthesized. The corresponding oxorhenium and [99gTc]oxotechnetium complexes prepared at the macroscopic level and chemically characterized were used for structure assignment of [99mTc](SNS/S) complexes prepared at the nanomolar level. Enzymatic hydrolysis of the pendant ester group of [99mTc](SNS/S) mixed ligand complexes by esterase was investigated in vitro and compared with that of the ethyl cysteinate dimer, [99mTc]ECD. Preliminary biodistribution data in mice shows that the complexes are lipophilic and exhibit significant initial uptake in rodent brain.

Animals↗
PubMed1998

Paratubal cysts in young females as an incidental finding in laparotomies performed for right lower quadrant abdominal pain.

Paratubal cysts represent remnants of the paramesonephric or mesonephric duct, the former being more common. Most of them are asymptomatic, but they may rarely give rise to clinical problems due to enlargement or torsion. In this study, we looked for paratubal cysts or other pathological lesions of the right uterine adnexa in young females operated upon for right lower quadrant (RLQ) abdominal pain. Our material consisted of 338 white female patients aged 4-14 years. Laparotomy revealed only acute appendicitis in 283 cases, while 44 had acute appendicitis plus a coincidental paratubal cyst. Most of these cysts were smaller than 1 cm in diameter. However, 2 additional cases had torsion of a large paratubal cyst, while 5 had a ruptured corpus luteum. We suggest that a thorough search of the right adnexa for the presence of paratubal cysts during laparotomies performed for RLQ pain is a useful procedure. This approach also allows detection of other pathological lesions of the right adnexa that often produce symptoms similar to acute appendicitis.

Abdomen, Acute↗
PubMed1997

Novel 99mTc aminobisthiolato/monothiolato "3 + 1" mixed ligand complexes: structure-activity relationships and preliminary in vivo validation as brain blood flow imaging agents.

A series of neutral, lipophilic 99mTc mixed-ligand complexes of the general formula 99mTcOL1L2, where L1H2 is an N-substituted bis-(2-mercaptoethyl)amine, [X-CH2CH2N(CH2CH2SH)2], [SNS], and L2H is a monodentate thiol (RSH), [S], has been synthesized and evaluated in rodents for potential use in brain blood flow imaging. The complexes were prepared by ligand exchange reaction using 99mTc(V)O-glucoheptonate as precursor and equimolar quantities of the two ligands. In all cases the syn isomer was formed in a high yield, whereas the anti isomer was not always present. The formation of two isomeric complexes-syn and anti-was expected, since the N-substituent (X-CH2CH2N) can assume syn or anti configuration with respect to the 99mTcO3+ core during complexation. One anti and all syn isomers were isolated by HPLC. Their identity was confirmed by comparative HPLC studies with the analogous 99Tc complexes of established structure. In vivo distribution, in particular brain uptake and retention, greatly depended on the type of either tridentate (L1H2) or monodentate (L2H) ligand. All 99mTc complexes showed significant brain uptake in mice (0.78-4.35% injected dose per organ at 5 min postinjection). This initial uptake remained nearly constant for at least 30 min for most of the complexes. Structure-activity relationships of novel 99mTc(V)O SNS/S complexes in mice are reported and discussed. Selected complexes were further studied in rats. High brain uptake, comparable to that of 99mTc-d,l-HMPAO, and sufficient retention 60 min postinjection were provided with complex 18 [X = (C2H5)2N and R = p-CH3OC6H4CH2].

Animals↗
PubMed1994

Tridentate ligands containing the SNS donor atom set as a novel backbone for the development of technetium brain-imaging agents.

In developing 99mTc complexes as potential brain-imaging agents, we investigated the coordination chemistry of ligands containing sulfur and nitrogen donor atoms with the general formula R-CH2CH2N(CH2CH2SH)2 (R = C2H5S, (C2H5)2N). These ligands act as tridentate SNS chelates to the TcO3+ core, leaving open one coordination site cis to the oxo group. In reactions with the highly reactive [99TcOCl4]- precursor, this vacancy was occupied by a chlorine atom. When the ligands reacted in the presence of 4-methoxythiophenol, using 99Tc(V)-gluconate as precursor, the vacancy was filled with 4-methoxythiophenol, which acted as coligand. Thus neutral mixed ligand complexes of the general formula [TcO((SCH2CH2)2NCH2CH2R)X], where X = Cl or 4-methoxythiophenol, were synthesized. The complexes were characterized by UV-vis, IR, 1H NMR, crystallographic, and elemental analyses. The crystal structures of 3a (R = C2H5S, X = Cl) and 4b (R = (C2H5)2N, X = 4-methoxythiophenol) demonstrated that the coordination geometry is trigonal bipyramidal with the N1 and Cl or S3 occupying the apical positions and the basal plane defined by the S1 and S2 of the tridentate ligand and the oxo group. The complexes 4a(99mTc) (R = C2H5S, X = 4-methoxythiophenol) and 4b(99mTc) were prepared using 99mTc-glucoheptonate as precursor and were purified by HPLC. Biodistribution in mice showed high initial brain uptake (3.68% and 3.56% dose/organ for 4a(99mTc) and 4b(99m-Tc), respectively). Complex 4b(99mTc) displayed significantly higher brain/blood values and prolonged retention in brain as well. The results suggest that structural modifications based on configurations 4a,b may provide novel 99mTc brain-imaging agents with improved biological characteristics.

Animals↗
PubMed1980

A foreign body in the palate.

A patient presented with a large cystic lesion in the palate in which there appeared to be a foreign body. The possible pathogenesis of the lesion is discussed.

Adult↗