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At least 325 records · Page 18Linked to original sources
PubMed1985

The design of a pentavalent 99mTc-dimercaptosuccinate complex as a tumor imaging agent.

In our search for a technetium-tumor seeking agent, the chemical characteristic of polynuclear Ga-citrate attracted our attention. On this basis, we selected the ligand dimercaptosuccinic acid (DMS) and appropriate labeling conditions in the design of 99mTc(V)-DMS. Chemical characterization was performed by thin layer chromatography, electrophoresis, Sephadex column chromatography and spectrophotometric studies at the chemical concentration (99Tc). Biodistribution in mice bearing Ehrlich ascites tumor and scintigraphic images in VX-2 tumor-bearing rabbit, indicated the great applicability of 99mTc(V)-DMS as a new tumor imaging agent. Its distinctive characteristic, different from the kidney imaging agent (99mTc-DMSA) is demonstrated and the biological implication of hydrolytic polynucleation of pentavalent technetium, through an anionic specie Tc(V)O3-(4), in the tumor cell is discussed.

Animals↗
PubMed1982

Biological chelation: 2,3-dimercapto-propanesulfonic acid and meso-dimercaptosuccinic acid.

Water soluble analogs of British Anti-Lewisite that are active orally and less toxic than BAL are now available. These agents are 2,3-dimercapto-1-propanesulfonic acid and meso-dimercaptosuccinic acid. Evidence for their effectiveness in preventing the lethal effects of sodium arsenite in mice and lewisite in rabbits is presented. These analogs can be expected to replace BAL in the treatment of heavy metal poisoning.

Animals↗
PubMed1983

99mTc-DMSA scanning to diagnose pyelonephritic scarring in children.

99mTechnetium-labeled dimercaptosuccinic acid (99mTc-DMSA) scanning provides superior quality images of renal parenchymal detail, which makes it highly sensitive for the diagnosis of pyelonephritic scarring. Unlike most other imaging techniques, radionuclide scanning is not affected by bowel gas or bony structures overlying the kidneys. This makes it particularly useful in children. Furthermore, renal scarring can be demonstrated by 99mTc-DMSA even before the classic gross anatomic and radiologic changes are present. The use of 99mTc-DMSA scanning in over 300 children has demonstrated its benefits and advantages over standard radiographic techniques.

Adolescent↗
PubMed1985

Clinical evaluation of 99mTc-DMSA renogram.

Two hundred-two 99mTc-DMSA renograms for urologic problems were evaluated. Some technical aspects of the examination and the value of the scintigraphic depth estimation are discussed. Pre- and postoperative uptake values in patients with renal surgery and sequential postoperative examinations are considered. The value of DMSA renograms in predicting recovery in obstructive uropathy and in deciding to opt for conservative therapy or nephrectomy is discussed.

Aged↗
PubMed1988

Technetium-99m dimercaptosuccinic acid uptake in long-term catheterized kidney. Comparison with renal function.

We studied 23 long-term catheterized kidneys in 14 patients. The uptake of 99mtechnetium dimercaptosuccinic acid (99mTc-DMSA) was measured at one- and two-hour intervals after injection, and the uptake was corrected for variations in renal depth. These values were compared with inulin, creatinine, and para-amino hippurate (PAH) clearances which were measured in each kidney by collecting urine through long-term catheterization. Correlation coefficient was obtained between PAH clearance corrected for the body surface area and the two-hour uptake of 99mTc-DMSA. The correlation coefficients between the two-hour uptake of 99mTc-DMSA and the clearance values are not significantly different from those between the one-hour uptake and the clearance values. Corrections of the uptake for variations in renal depth did not improve the correlation coefficients. The results show that 99mTc-DMSA is an excellent method to estimate the renal plasma flow and the one-hour uptake without correction for renal depth is clinically sufficient to evaluate the split renal function.

Aged↗
PubMed1991

Effect of extracorporeal piezoelectric lithotripsy shock waves on renal function measured by Tc-99m-DMSA using SPECT.

Extracorporeal shock-wave lithotripsy has altered the therapeutic approach to urinary stone disease. Recently, a method was developed in which shock-wave generation is obtained piezoelectrically. To evaluate the effect of extracorporeal piezoelectric lithotripsy (EPL) on renal function, 20 patients were studied prior to and after EPL of renal calculi. Renal cortical function was evaluated by using a previously described and validated quantitative single photon emission computerized tomography (SPECT) method to measure individual absolute uptake of technetium-99m dimercaptosuccinic acid (Tc-99m-DMSA). Twenty kidneys were treated, and the 19 contralateral kidneys were without stone disease (1 patient had a single kidney). The absolute kidney uptake of Tc-DMSA in the normal kidneys was 21.4% +/- 6.2% before and 22.2% +/- 6.4% after EPL. For the treated kidneys the absolute update was 16.8% +/- 5.3% and 16.8% +/- 4.7% before and after, respectively. There was no statistical significant difference between pre- and post-treatment values. The absolute kidney uptake was significantly lower (p less than 0.01) in the treated than in the normal kidneys. This study indicates that the EPL procedure did not cause any damage to cortical function detectable by the DMSA uptake.

Adult↗
PubMed1984

Octanol/water partition coefficients as a model system for assessing antidotes for methylmercury(II) poisoning, and for studying mercurials with medicinal applications.

1-Octanol/water partition coefficients, [HgII]octanol/[HgII]water, provide a simple but limited model system for aspects of the biological behavior of methylmercury(II) and commonly used organomercury(II) medicinal compounds. In an octanol/water system some widely studied antidotes for mercury poisoning at least partly displace the biological thiols L-cysteine and glutathione from binding to MeHgII at pH 6.9. Addition of the antidote meso-dimercaptosuccinic acid to MeHgII in the presence of glutathione results in formation of metallic mercury. For RHgII derivatives of L-cysteine and glutathione, octanol/water partition coefficients follow the order Ph greater than Et greater than Me. An exceptionally high value for diphenylmercury, compared with PhHgII derivatives of L-cysteine and glutathione, is consistent with reported results of the distribution of mercury compounds in rats. Ethylmercury(II) is partly displaced from thimerosal by L-cysteine and glutathione in the octanol/water system, indicating that the active form of thimerosal in vivo may involve binding of EtHgII to biological ligands.

Animals↗
PubMed1989

Lead chelates of meso- and racemic-dimercaptosuccinic acid.

Lead chelates of racemic- and meso-dimercaptosuccinic acid (DMSA) were synthesized and isolated from aqueous solutions and characterized by potentiometric measurements and infrared spectroscopy. Two types of lead chelates of racemic DMSA were isolated: one in which racemic-DMSA is coordinated to Pb+2 via one oxygen and one sulfur atom and the other in which the Pb2+ is coordinated via two sulfur atoms. The latter form of the chelate is converted into the former upon dissolution in dimethylsulfoxide. Only one type of Pb2+ chelate of the meso form of the ligand was formed. In this case, meso-DMSA is coordinated to Pb+2 via one oxygen and one sulfur atom. Meso- and racemic-DMSA have very different solubilities in aqueous solutions. Meso-DMSA is slightly soluble in water, whereas racemic-DMSA is very soluble in water even in the presence of strong acids. The solubilities of the chelates were found to be pH dependent. When the uncoordinated sulfhydryl and carboxylic acid groups dissociate, the chelates dissolve and remain in aqueous solution. The infrared spectra of meso- and racemic-DMSA show distinct features that can be used to detect the presence of either diastereoisomer.

Chelating Agents↗
PubMedDate not supplied

Imaging modalities in the follow-up of non-iodine avid thyroid carcinoma.

INTRODUCTION: The treatment of primary thyroid cancer requires protracted follow-up because of to the possibility of the development of recurrent metastases many years after the initial diagnosis. Often such follow-up involves imaging at regular intervals with diagnostic I-131 studies. However, not all thyroid cancer concentrates I-131. The purpose of this article is to review the efficacy of alternative diagnostic imaging modalities for follow-up of thyroid carcinomas that do not concentrate radioiodine. MATERIALS AND METHODS: These procedures include the use of nuclear medicine imaging with thallium-201 (TI-201), Tc-99m-sestamibi, Tc-99m pentavalent dimercaptosuccinic acid (DMSA), radiolabeled anti-carcinoembryonic antigen antibodies, and radioiodinated-131 meta-iodobenzyl guanidine, as well as computerized x-ray tomography, magnetic resonance imaging (MRI), and ultrasound (US). RESULTS AND CONCLUSION: Thallium-201, MRI, and pentavalent DMSA provide adequate sensitivity for follow-up of selected patients with suspected recurrent noniodine concentrating thyroid carcinoma.

3-Iodobenzylguanidine↗
PubMed1984

DMSA, DMPS, and DMPA--as arsenic antidotes.

meso-Dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS), and N-(2,3- dimercaptopropyl )- phthalamidic acid (DMPA) are water soluble analogs of 2,3-dimercapto-1-propanol (BAL). The relative effectiveness or therapeutic index of these dimercapto compounds in protecting mice from the lethal effects of an LD99 of sodium arsenite is DMSA greater than DMPS greater than DMPA greater than BAL in the magnitude of 42:14:4:1, respectively. DMPS, DMPA, or DMSA will mobilize tissue arsenic. BAL, however, increases the arsenic content of the brain of rabbits injected with sodium arsenite. These results raise the question as to the appropriateness of BAL as the treatment for systemic arsenic poisoning. Either DMSA or DMPS, when given sc or po, will protect rabbits against the lethal systemic effects of subcutaneously administered Lewisite . DMPS and DMSA have promise as prophylactics for the prevention of the vesicant action of Lewisite . The sodium arsenite inhibition of the pyruvate dehydrogenase (PDH) complex can be prevented and reversed in vitro or in vivo by DMPS, DMSA, DMPA, or BAL. Of them all, DMPS is most potent and BAL appears to be the least potent. The usefulness of all these dimercapto compounds would be enhanced by a careful study of their metabolism and biotransformation. These dimercapto compounds are in a great many respects orphan drugs. At this stage of their development, it is very difficult for the clinician to obtain funds to study them clinically even though they appear to be useful for treatment of poisoning by any one of the heavy metals.

Animals↗
PubMed1988

Behavioral consequences of chelator administration in acute cadmium toxicity.

The conditioned flavor-aversion paradigm was used to assess the toxicity of acutely administered cadmium and the interaction of cadmium with the heavy-metal chelating agents dimercaprol (BAL) and dimercaptosuccinic acid (DMSA). Shortly after consuming saccharin, rats received ip administration of cadmium either alone or in combination with sc administration of BAL or DMSA. Three days later they were given the choice between consuming saccharin or water, and saccharin preferences were recorded. When compared to rats receiving either nothing or the vehicle, rats receiving cadmium displayed significant reductions in saccharin preference (i.e., conditioned flavor aversions). BAL and DMSA were also capable of producing conditioned flavor aversions when given alone. Rats receiving cadmium in combination with either BAL or DMSA displayed significant, but not complete attenuations of conditioned flavor aversions when compared to the flavor aversions of rats receiving cadmium alone. Chelator-induced blockade of cadmium-induced flavor-aversion conditioning was not obtained when BAL or DMSA administration was delayed by 4 hr. Attenuation of cadmium-induced aversions by BAL and DMSA extends earlier findings of an attenuation of lead-induced flavor-aversion conditioning by these complexing agents, and thus demonstrates further the utility of the flavor-aversion conditioning paradigm in characterizing metal-chelator interactions.

Animals↗
PubMed1988

Developmental toxicity of subcutaneously administered meso-2,3-dimercaptosuccinic acid in mice.

meso-2,3-Dimercaptosuccinic acid (DMSA) is a water-soluble effective antidote for the treatment of heavy-metal intoxications. Information concerning the developmental toxicity of DMSA, however, has not been available. In order to determine the potential developmental toxicity of DMSA, pregnant Swiss mice were given 0, 410, 820, or 1640 mg DMSA/kg/day subcutaneously on Days 6-15 of gestation. Maternal effects included a significant reduction in weight gain during the exposure and postexposure periods at 1640 mg/kg/day. Food consumption was similar to controls at all doses levels except for the high dose group in the post-treatment period. Results of hematological and serum biochemical analyses in the DMSA-treated groups were comparable to those of the controls. However, in light of the pronounced effects on maternal weight gain the dose of 1640 mg/kg/day would be maternally toxic. Significant increases in the number of resorptions and the incidence of stunting were found, along with a significant decrease in the number of live fetuses per litter, when the 1640 mg/kg/day group was compared with the controls. Significant reductions in fetal body weight and fetal body length means were also found when the 820 and 1640 mg/kg/day groups were compared with the controls. Consequently, these results indicate that DMSA would be embryo-toxic to mice at 1640 mg/kg/day and fetotoxic at 820 mg/kg/day. In contrast, very slight fetotoxicity was observed at 410 mg/kg/day. Gross external, internal soft tissue, and skeletal examinations of the fetuses revealed that DMSA was teratogenic in the mouse when given subcutaneously at 820 and 1640 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Determination and metabolism of dithiol chelating agents. VII. Biliary excretion of dithiols and their interactions with cadmium and metallothionein.

N-(2,3-Dimercaptopropyl) phthalamidic acid (DMPA), meso-dimercaptosuccinic acid (DMSA), and 2,3-dimercapto-1-propanesulfonic acid (DMPS) are dithiol chelating agents with antidotal activity for lead, mercury, arsenic, and other heavy metals. The biliary excretion of these compounds was studied in male Sprague-Dawley rats. After iv administration of DMPA, 72% of the injected dose was recovered in the bile. Half of the recovered DMPA was in the unaltered form (parent compound) and the other half was in the altered form (parent compound recovered after chemical reduction by DTT). An altered, presumably disulfide, form of DMPS was found in the bile. Neither unaltered nor altered DMSA was detected in the bile. DMPA (0.10 mmol/kg), given to rats 3 days after exposure to Cd, elicited within 30 min a 20-fold increase in biliary Cd excretion. The increase of biliary Cd by DMPA was dose-related and not due to an increase of bile flow rate. DMSA and DMPS did not significantly affect the biliary excretion of Cd. Incubation of DMPA or DMSA with Cd-saturated metallothionein (MT) resulted in the removal of Cd from MT. DMPA was more active than DMSA in this respect. The evidence strongly supports the mechanism that the increase of biliary cadmium following DMPA administration is the result of DMPA entering cells and mobilizing and removing the cadmium from MT. The removal of cadmium from metallothionein by dithiol chelating agents provides another dimension to their mechanisms of action and may provide an important new tool for the study of cadmium as well as metallothionein.

Animals↗