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Biomedical subjects

R Alberto

Publications and source records attributed to R Alberto.

At least 19 recordsLinked to original sources
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↗
PubMed2005

Relative stability of mixed [3 + 1] Tc and Re complexes: a computational and conceptual DFT study.

A computational and conceptual density-functional study has been performed on various [3 + 1] complexes of both Re(V) and Tc(V). The fully optimized complexes chloro(3-thiapentane-1,5-dithiolato)oxorhenium(V) and chloro(3-thiapentane-1,5-dithiolato)oxotechnetium(V) show geometries that compare favorably with the X-ray data. These structures were used as a starting point to investigate the relative stability of Tc(V) and Re(V) complexes with various ligands containing combinations of N, O, and S as chelating atoms and to evaluate the stabilizing/destabilizing influence of these N, O, and S combinations. For both Tc and Re complexes, the S content (number and position of S atoms) together with the presence of an oxygen as the central chelating atom turns out to be decisive in the stability of the tridentate complexes, the latter factor being strongly destabilizing and the former stabilizing. The stabilization sequences for both Tc and Re are shown to be identical in the gas phase and in aqueous solutions treated in a polarizable continuum model. The Re(V) complexes are found to be more stable than their Tc(V) analogues. All of the results are successfully interpreted in terms of the hard and soft acids and bases principle, applied at the local level. For this purpose, a softness value for Tc is obtained by interpolating softness trends in neighboring elements of rows 5 and 6 in the periodic table.

Journal Article↗
PubMed2004

Operative files of legal medical emergency in Calabria: study team.

In Calabria, a study team form legal medicine emergency (LME) formed to initiate a Crisis Unit (CU) able to manage and deal LME with complicated operations and roles, people and technical aspects involvement. First steps are planning, scene study and organization. Everything connecting the first and second emergency to have practicable application.

Disasters↗
PubMed2001

Re tricarbonyl complexes with ligands containing P,N,N and P,N,O donor atom sets: synthesis and structural characterization.

The coordination chemistry of the heterofunctionalized phosphines HPN2 and H2PNO and of an analogue containing a relevant biomolecule, HPN-Pip (Pip = 4-(3-aminopropyl)-1-(2-methoxyphenyl)piperazine), was studied toward the synthon (NE4)2[ReBr3(CO)3]. The complexes isolated, [Re(CO)3(kappa(3)-PN2)], 3, [Re(CO)3Br(kappa(2)-H2PNO)], 4, and [Re(CO)3Br(kappa(2)-HPN-Pip)], 5, are the first examples of Re(I) compounds stabilized by such a combination of donor atoms. All of the compounds are neutral, but the phosphines, depending on the combination of atoms, act as monoanionic and tridentate (3) or as neutral and bidentate (4, 5). The characterization of 3-5 included IR, 1H NMR, and 31P NMR spectroscopy and X-ray crystallographic analysis. Colorless crystals of compounds 3 and 4 were obtained by slow evaporation of a methanolic solution of 3 and from a boiling acetonitrile solution of 4. Compound 3 crystallizes with two molecules of MeOH per asymmetric unit in the monoclinic space group P2(1)/c, a = 10.1237(8) A, b = 9.4959(4) A, c = 28.365(2) A, beta = 98.707(9) degrees, V = 2695.4(3) A(3), Z = 4; 4 crystallizes in the triclinic space group Ponebar, a = 10.0241(9) A, b = 11.2060(10) A, c = 13.0656(12) A, alpha = 84.883(11) degrees, beta = 71.163(10) degrees, gamma = 63.650(9) degrees, V = 1241.19(19) A(3), Z = 2.

Crystallography, X-Ray↗
PubMed2001

Derivatization of glucose and 2-deoxyglucose for transition metal complexation: substitution reactions with organometallic 99mTc and Re precursors and fundamental NMR investigations.

Synthetic strategies for the bifunctionalization of glucose and 2-deoxyglucose at position C-1 for transition metal coordination are reported. In particular organometallic technetium and rhenium complexes for potential use in diagnostic nuclear medicine were synthesized and investigated. Specifically, a common iminodiacetic acid (IDA) moiety was O-glycosidically connected through an ethylene spacer group to produce the pure alpha- (in case of 2-deoxyglucose) and beta-anomer (in case of glucose). Reaction of the sugar derivatives with the organometallic precursor [M(H2O)3(CO)3]+ (M = 99mTc, Re) produced single products in high yield, which are water-soluble and water-stable. The displacement of the three water molecules of the metal precursor and thus the tridentate coordination of the metal-tricarbonyl core exclusively via the amine and the two carboxylic acid functionalities of the IDA chelate was verified by means of 1D and 2D 1H NMR spectroscopy, mass spectrometry, and IR spectroscopy. The radioactive-labeled products (99mTc) proved their excellent stability in vitro in physiological phosphate buffer (pH = 7.4) and human plasma over a period of 24 h at 37 degrees C.

Deoxyglucose↗
PubMed2001

Aqueous One-Pot Synthesis of Derivatized Cyclopentadienyl-Tricarbonyl Complexes of (99m) Tc with an In Situ CO Source: Application to a Serotonergic Receptor Ligand.

Instant radiopharmaceuticals-just add [(99m) TcO4 ](-) in water! Half-sandwich complexes of the type [(RCOCp)(99m) Tc(CO)3 ] (e.g. 1) were synthesized in a single step in water from [(99m) TcO4 ](-) . The acidification of the Cp ring by a carbonyl substituent and the use of K2 [H3 BCO2 ] as a reducing agent and in situ source of CO are instrumental in the synthesis.

carbonylation↗
PubMed2001

Surfactant protein B labelled with [(99m)Tc(CO)3(H20)3](+) retains biological activity in vitro..

UNLABELLED: Labelling of the hydrophobic surfactant protein B (SP-B) under non-reducing conditions was achieved with [(99m)Tc(CO)(3)(H2O)(3)](+) prepared according to Alberto et al. (JACS, 1998). The binding of radioactivity was protein-specific, with an overall radiochemical yield of 50%. Gel electrophoresis and Westernblot analyses showed no structural changes of SP-B. Spreading properties and surface activity of (99m)Tc-labelled SP-B in an air/water interface coincided with those of unlabelled SP-B. (99m)Tc-SP-B seems to be a promising agent to observe surfactant spreading under clinical conditions. BACKGROUND: Therapeutic results for surfactant instillation in clinical trials are conflicting. The (99m)Tc-labelling of surfactant would allow to observe its spreading in the lung under clinical conditions. METHODS: [(99m)Tc(CO)(3)(H2O)(3)](+) was prepared as described by Alberto et al. (JACS, 1998). This carbonyl complex was used for the direct labelling of surfactant protein B (SP-B) under non-reductive conditions by direct incubation with SP-B at elevated temperature followed by extraction into CHCl(3)/MeOH. RESULTS: The hydrophobic protein SP-B was labelled with [(99m)Tc(CO)(3)(H2O)(3)](+). An overall radiochemical yield of about 50% was achieved. HPLC-analysis revealed a single radiolabelled species according to UV elution profile of SP-B, supported by paper and size exclusion chromatography. Gel electrophoresis confirmed that the dimer structure of SP-B was preserved. Spreading properties of (99m)Tc-labelled SP-B in an air/water interface coincided with those of unlabelled SP-B. Spreading of radioactivity observed in a glass trough of 26 cm x 27 cm with a gamma camera was completed during the first 7-9 sec after application of (99m)Tc-labelled SP-B. The corresponding decrease of surface tension to 45 mN/m at the peripheral surface tension sensors took 7 sec +/- 2 sec (MEAN +/- STD; n = 3). CONCLUSIONS: Direct and specific (99m)Tc-labelling of the hydrophobic surfactant protein B was achieved using the [(99m)Tc(CO)(3)(H2O)(3)](+) precursor. This procedure can easily be used to prepare specifically labelled surfactant mixtures with spreading properties that coincide with those of unlabelled surfactant.

Animals↗
PubMed2001

Dicarbonyl-nitrosyl-complexes of rhenium (Re) and technetium (Tc), a potentially new class of compounds for the direct radiolabeling of biomolecules.

Re- and Tc-complexes of the oxidation state (+I) offer a useful synthetic pool for the labeling of biomolecules due to their co-ordination properties and stability, which are superior to compounds of the oxidation state (+V). Based on the results for Tc-tricarbonyl complexes it was the topic of this work to develop an access to similar but higher charged compounds, which could be performed by replacing a neutral [CO]-group by a [NO](+)-group. The resulting Re(I)- and Tc(I)-dicarbonyl-nitrosyl complexes, such as [N(CH2CH3)4][ReX3(CO)2(NO)], show a tendency for co-ordination at carboxylic and amine groups of biomolecules (X = Br, Cl). This was shown with picolinic acid (H-pic), a suitable model for amino acids, forming the neutral complex [ReX(pic)(CO)2(NO)]. In a similar fashion conjugation of [188Re(CO)2(NO)](2+)- or [99mTc(CO)2(NO)](2+)-compounds to proteins or antibodies is feasible. This approach opens a way to a potentially new class of radiopharmaceuticals.

Isotope Labeling↗
PubMed2000

Complete Carbonylation of fac-

The rate constant of ligand exchange on the complex fac-[(99)Tc(H(2)O)(3)(CO)(3)](+) was determined by means of (13)C, (17)O, and (99)Tc NMR spectroscopy under pressurized conditions in aqueous media. After keeping the sample under CO pressure for an extended period, the formation of [(99)Tc(CO)(6)](+) could unambiguously be detected in the (13)C and (99)Tc NMR spectra.

Journal Article↗
PubMed1999

In vitro and in vivo evaluation of bidentate, water-soluble phosphine ligands as anchor groups for the organometallic fac-[99mTc(CO)3]+-core.

The organometallic precursor fac-[99mTc(OH2)3(CO)3]+, 1a, was reacted with the bidentate, water-soluble phosphine ligands bis(bis(hydroxymethyl)phosphino)ethane (HMPE) and bis(bis(hydroxymethyl)phosphino)benzene (HMPB) in 0.9% saline to produce complexes in >95% yields. High performance liquid chromatography analyses indicate the initial formation of the complexes fac-[99mTcCl(CO)3L] (L = HMPE 2a, HMPB 3a). The neutral complexes ultimately lose the coordinated chloride to produce the cationic species fac-[99mTc(OH2)(CO)3L]+ 2b/3b. In vitro studies showed a high stability of 2b/3b over a wide pH range for >24 h. No decomposition or alteration of the complexes was observed even in the presence of excess histidine, cysteine, or human serum albumin. Experiments performed in normal mice demonstrated a fast clearance of the cationic compounds 2b/3b from the blood pool and clearance through the hepatobiliary and the urinary pathways.

Animals↗
PubMed1999

Rhodium-105 tetrathioether complexes: radiochemistry and initial biological evaluation.

105Rhodium(III) complexes with three different acyclic tetrathioether ligands containing pendant carboxylic acid groups have been synthesized and characterized. The complexes were evaluated for stability under physiological conditions and the most promising complexes were evaluated in vivo in normal mice. The primary route of clearance for these complexes was the renal/urinary system, consistent with the presence of pendant carboxylate groups. The results indicate that the cis-[Rh(III)Cl2(2,5,8,11-tetrathiadodecane-1,12-dicarboxylic acid)]+ complex shows the most promising in vivo characteristics on which to base a potential therapeutic radiopharmaceutical.

Animals↗
PubMed1999

Stable one-step technetium-99m labeling of His-tagged recombinant proteins with a novel Tc(I)-carbonyl complex.

We have developed a technetium labeling technology based on a new organometallic chemistry, which involves simple mixing of the novel reagent, a 99m Tc(I)-carbonyl compound, with a His-tagged recombinant protein. This method obviates the labeling of unpaired engineered cysteines, which frequently create problems in large-scale expression and storage of disulfide-containing proteins. In this study, we labeled antibody single-chain Fv fragments to high specific activities (90 mCi/mg), and the label was very stable to serum and all other challenges tested. The pharmacokinetic characteristics were indistinguishable from iodinated scFv fragments, and thus scFV fragments labeled by the new method will be suitable for biodistribution studies. This novel labeling method should be applicable not only to diagnostic imaging with 99mTc, but also to radioimmunotherapy approaches with 186/188 Re, and its use can be easily extended to almost any recombinant protein or synthetic peptide.

Aldehydes↗
PubMed1999

Catabolism of neurotensins. Implications for the design of radiolabeling strategies of peptides.

A major impact in diagnosis and treatment of cancer with peptide based radiopharmaceuticals is expected. Among others neurotensin is considered to be a promising candidate. However, most neurotensin analogues, which bind to the neurotensin receptor have a too short biological half live due to catabolism. Therefore, stabilized fragments have been prepared and labeled with the newly developed [Tc(CO)3](+)-moiety. A single histidine or a (N alpha-His)-Ac group coupled to the N-terminus of the neurotensin fragments were used as a bidentate or a tridentate ligand respectively, which coordinate the metal carbonyl efficiently. Affinity and binding studies of the 99mTc(I) radiolabeled neurotensin fragments revealed a behavior influenced by catabolism and properties of the metal complex.

Affinity Labels↗
PubMed1999

Organometallic 99mTc-aquaion labels peptide to an unprecedented high specific activity.

UNLABELLED: A new peptide labeling method that uses the organometallic aquaion [99mTc(H2O)3(CO)3]+ has been developed. METHODS: A selection of amino acids was labeled at different concentrations with the organometallic aquaion, and the labeling yield was determined by high-performance liquid chromatography. This investigation has shown histidine to be a very potent ligand, with specific activities of up to 6 TBq/micromol (160 Ci/micromol) ligand. Histidine derivatives have been coupled to neurotensin(8-13) (NT[8-13]) and have been labeled with the aquaion, resulting in high specific activities with (N(alpha)-histidinyl)acetic acid-NT(8-13) similar to those with histidine. RESULTS: Histidine derivatives of NT(8-13) labeled using this approach fully retained their receptor affinity, showing KD values of all investigated NT analogs below 1 nmol/L on colon carcinoma HT29 cells. Biodistrbution experiments in BALB/c mice showed complete clearance of (N(alpha)-histidinyl)acetic acid-NT(8-13) from the blood after 24 h and no unwanted accumulation in any tissue. CONCLUSION: The novel labeling method using the organometallic 99mTc-aquaion combines the advantage of highest specific activities with minimal functionalization of proteins and peptides under retention of biologic affinity.

Animals↗
PubMed1994

Influence of radiolabel on the in vivo processing of intact and fragmented anti-tumour monoclonal antibody.

The anti-colon carcinoma MoAb35 and its F(ab')2 fragment were labelled with 131I or 67Cu and their biodistributions compared in nude mice bearing human tumour xenografts. Two-fold higher levels of 67Cu were found in the xenografts than 131I, with no significant difference in whole-body distribution. For the F(ab')2 fragment tumour levels were not significantly different between 131I and 67Cu. A very high accumulation of 67Cu was found in the kidney (36.7% ID/g). Whether deiodination in the kidney could account for the difference in nuclide accumulation was checked by repeating the study with 131I, linked to the F(ab')2 by a method known to resist deiodination. The results showed a slight increase in tumour accumulation of 131I but kidney levels remained low at 3.1% ID/g 24 hours post-injection compared to 42.4% ID/g for 67Cu, suggesting that deiodination does not play a role in the observed low levels of 131I in the kidney. Ongoing studies on the distribution and processing of radioimmunoconjugates will hopefully assist in their application in clinical studies.

Animals↗