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Biomedical subjects

C L de Ligny

Publications and source records attributed to C L de Ligny.

At least 19 recordsLinked to original sources
PubMed1993

Investigation of two new [99mTc]Tc-HEDP preparations that can be expected to give a better lesion-to-normal-bone uptake ratio when used as bone scanning agents.

Two new potential bone scanning agents have been prepared and characterized. One of the agents, Tc(Sn,pH 12)-HEDP, is prepared at pH 12 (and subsequently neutralized). The other agent, Tc(Fe)-HEDP, is prepared by reducing [99mTc]TcO4- by a mixture of Fe(II) and Sn(II). From ion exchange chromatography on Aminex A-28 it appeared that the proportion of early eluting components of the two new agents is larger than that of the usual agent, Tc(Sn,pH 7.4)-HEDP. The stabilities on storage, and in serum, of the three agents appeared to be equally good. The adsorption on tri-calciumphosphate of Tc(Fe)-HEDP and Tc(Sn,pH 7.4)-HEDP was determined at several values of concentrations of Sn(II) and HEDP. Further, the influence of the pH (1-12) during reduction of [99mTc]TcO4- by Sn(II) on the adsorption of the agent on tri-calciumphosphate (at a fixed pH of 7.4) was investigated. It appeared that the adsorption of Tc(Sn,pH 12)-HEDP and Tc(Fe)-HEDP is less than that of Tc(Sn,pH 7.4)-HEDP. It is argued that this result points to a better efficiency in lesion detection of the two new agents, compared to the usual one.

Adsorption↗
PubMed1989

The binding of 99mTc(Sn)-MDP complexes to human serum albumin and other blood proteins determined with gel chromatography and ultrafiltration.

The binding of 99mTc(Sn)-MDP to human serum albumin and other blood proteins was investigated by gel chromatography and ultrafiltration. During gel chromatography dissociation of the 99mTc(Sn)-MDP-protein complex occurs: thus, it is not a suitable technique for the determination of protein binding. The values found with ultrafiltration have to be corrected for non-ultrafiltrable TcO2.nH2O. From the corrected values it can be concluded that binding of 99mTc(Sn)-MDP to blood proteins does not play a role in the biodistribution.

Blood Proteins↗
PubMed1989

Improvement of the reproducibility of ion-pair HPLC of 99mTc(Sn)EHDP complexes and the influence of the Sn(II) concentration on the composition of the reaction mixture.

The use of a non-volatile modifier and the simultaneous exclusion of oxygen by flushing with helium in ion-pair HPLC of 99mTc(Sn)EHDP-complexes prevents spurious oxidation during the separation process. It thus enables the omission of the reducing agent from the eluent solution and the determination of the labelling percentage from the TcO4(1)-peak. In addition, retention times become more reproducible.

Chromatography, High Pressure Liquid↗
PubMed1988

Anion exchange chromatography of 99mTc(Sn)-MDP complexes: influence of eluent composition, determination of void volume and charge of the main component.

99mTc(Sn)-MDP complexes have been prepared by reduction of 99mTcO4- by Sn(II) in the presence of MDP. These complexes were separated on an anion exchange column. The necessity of the addition of the ligand and the reducing agent to the eluent to avoid decomposition during chromatography is demonstrated. For the main component that is found at pH 5 the ionic charge was calculated according to the method of Wilson and Pinkerton [Anal. Chem. 57,246 (1985)] and the method of Russell and Bishoff [Int. J. Appl. Radiat. Isot. 35,859 (1985)]. With the first method a charge of -4.2 +/- 0.3 was obtained, with the second a charge of -5.1 +/- 0.6. An accurate method to determine the void volume of the ion exchange column is described.

Chromatography, Ion Exchange↗
PubMed1988

99mTc bone scanning agents--IV. Chemical characterization of 99mTc(Sn)-pyrophosphate complexes.

Various reaction mixtures for the preparation of 99Tc(Sn)-pyrophosphate were investigated by means of gel chromatography. All components were radioactively labeled. The most likely composition of the complexes, which also appear in "no carrier added" preparations, was determined. At pH 7 one complex is found with the composition TcPyp2. Two complexes are found at pH 4: TcPyp and TcPyp2. Further, at pH 7 a polymeric technetium compound is found not containing tin or pyrophosphate.

Bone and Bones↗
PubMed1987

The effect of the reduction method on the composition of 99mTc-EHDP complexes.

The composition of 99mTc-ethane-1-hydroxy-1, 1-diphosphonate complexes, prepared with the reducing agent NaBH4 and by electrolytic reduction, was analysed by reversed-phase ion-pair chromatography and soft-gel permeation chromatography. The results were compared with corresponding data for complexes prepared with the traditional reducing agent tin(II). Significant differences between the chromatograms of the three preparations were found. They were interpreted in terms of the occurrence of different complexes in the three preparations.

Chemical Phenomena↗
PubMed1987

Gel chromatographic analysis of the bone seeking radiopharmaceutical 99mTc(Sn)-EHDP: the influence of pH and EHDP-concentration on the size of its constituents.

99mTc(Sn)-EHDP complexes have been produced by reduction of TcO4- with Sn(II) in the presence of EHDP at varying pH and EHDP concentration. The mixture was separated by means of gel-chromatography with an eluent of the same composition and pH as the reaction mixture. It appears that at neutral pH larger complexes are formed than under acidic or basic reaction conditions. Larger complexes are also formed at higher EHDP concentrations.

Bone and Bones↗
PubMed1987

99mTc bone scanning agents--V. Influence of experimental conditions on the labeling efficiency and gel chromatography of 99mTc(Sn)HMDP.

The preparation of 99mTc(Sn)HMDP was investigated as a function of pH, Sn(II) and ligand concentration. HMDP could be labeled efficiently from pH 2-9. The Sn(II) and the ligand concentrations had a beneficial influence. The composition of the radiopharmaceutical under various experimental conditions was studied by means of gel chromatography on Biogel P-4. Six different complexes were found. A preparation consisted of maximally three major complexes. The presence of a particular complex was mainly determined by pH and ligand concentration. The Sn(II) concentration had little influence.

Bone and Bones↗
PubMed1986

The effect of DMSO treatment on the composition of 99mTc(Sn)EHDP.

To find an explanation for the reported positive effect of a dimethyl sulfoxide (DMSO) treatment on the performance of the bone scan agent technetium-(tin)-ethane-1-hydroxy-1, 1-diphosphonate, we compared the composition of the agent, prepared with and without treatment with DMSO by using high performance ion-pair chromatography (IPC). The preparation obtained with the DMSO treatment appeared to contain a larger fraction of large and highly charged polynuclear complexes than the preparation without the DMSO treatment. According to experiments by other investigators the smaller 99mTc(Sn)EHDP complexes (early eluting components in IPC) give lower bone/blood ratios than the larger ones. The results presented in this paper show that the explanation for the effect of the DMSO treatment may be that the Sn-EHDP complexes which are removed by extraction with DMSO, give relatively small 99mTc(Sn)EHDP complexes. Without these small complexes a superior bone scan agent is obtained. From experiments in which an excess of 99TcO4 over Sn(II) was used, it was concluded that at least one of the technetium complexes contains Sn(IV). On the other hand, the absence of Sn from a late eluting technetium complex was proven.

Bone and Bones↗
PubMed1986

The separation of 99mTc(Sn)EHDP complexes by HPLC and GPC.

For the characterization of the multi-component bone-scan agent 99mTc(Sn)EHDP we have analysed the complex mixture with reversed phase ion pair chromatography (IPC) and soft gel permeation chromatography (GPC). With IPC five major complexes were found within a separation-time of 40 min. To avoid decomposition of the complexes during separation, the concentrations of EHDP and the reductant Sn(II) in the eluent had to be identical to the EHDP and Sn(II) concentrations used for the preparation of the complexes. To investigate the stability of the complexes we applied separation by IPC, followed by re-analysis of the fractions within 1 h and after 21-25 h. It appears that there is a state of equilibrium between the five complexes. Within 1 h after isolation the separated complexes were still more than 90% in their original form while after 20 h considerable amounts of the other complexes are found. The two complexes with the largest retention time with IPC are the most stable ones. When the total mixture was re-analysed after 26 h all five components appeared to be still present, but the relative amount of the most stable component had increased. Using GPC for the separation of the complex mixture, we found four major peaks within a separation time of 14 h. The elution orders of the complexes with the two separation methods are opposite.

Bone and Bones↗
PubMed1986

99mTc bone scanning agents--II. Adsorption of 99mTc(Sn)pyrophosphate complexes on the mineral phase of bone.

The adsorption of pyrophosphate, tin-pyrophosphate and 99mTc(Sn)pyrophosphate on Ca3(PO4)2 was investigated at pH 4.0 and pH 7.4. All components were radioactively labeled. Tin and reduced technetium were in most cases almost completely bound. The adsorption of pyrophosphate, tin(II) and technetium-99m at pH 4.0 was higher than at pH 7.4. The presence of tin gave rise to an increase of the pyrophosphate adsorption that was much larger than can be accounted for by a stoichiometric adsorption of tin-pyrophosphate. It is concluded that tin and technetium are bound as negatively charged complexes with pyrophosphate. Finally it is argued that the fraction of the bone scanning agent that reaches the bone surface is adsorbed completely by the mineral phase.

Adsorption↗
PubMed1986

99mTc bone scanning agents--III. Preparation and gel chromatography of 99mTc(Sn)MDP complexes.

The preparation of 99mTc(Sn)MDP was investigated as a function of pH, MDP concentration and Sn(II) concentration. The labeling efficiency was over 90% in the majority of the experiments and remained constant over the range pH 2-9. The MDP concentration had little effect, while the Sn(II) concentration had a significant positive influence. The complex formation appeared to be partly reversible. The formation of different complexes was investigated by means of gel chromatography under various experimental conditions. Altogether six complexes were found. At acid conditions two major complexes were found and at neutral pH one major complex. The presence or absence of a particular complex was mainly determined by the pH and by the MDP concentration. The Sn(II) concentration had very little effect. The results are compared with previous results of similar experiments with 99mTc(Sn)pyrophosphate.

Bone and Bones↗