99mTc(V)-dimercaptosuccinic acid scintigraphy for medullary thyroid carcinoma.
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We performed 99mTc dimercaptosuccinic acid (DMSA) scan and ultrasonography in 146 children during the acute phase of a proven urinary tract infection (UTI). In 99 a micturating cysto-urethrography and in 83 an intravenous urography was also done. The occurrence of fever and increased WBC count, CRP and ESR were also studied. It appeared from this retrospective study that 47% of the kidneys had a cortical or patchy pattern of decreased uptake of 99mTc DMSA, as compared to 23% with abnormal findings on US. Vesico-ureteral reflux was present in 38% of the kidneys with parenchymal involvement on 99mTc DMSA scan. Although fever, leucocytosis and elevated CRP and ESR were significantly correlated with abnormal 99mTc DMSA scan, they were also observed in children without renal parenchymal involvement. Our results suggest that 99mTc DMSA scan is a sensitive method for the detection of parenchymal involvement during acute UTI. The exact nature of these lesions and their relation with scars need, however, to be defined.
The therapeutic efficacy of six newly synthesized analogues of dimercaptosuccinic acid (DMSA) was investigated in acute arsenic trioxide poisoning in mice. Meso-2,3-di(acetylthio)succinic acid (DATSA) and meso-2,3- di(benzoylthio)succinic acid (DBTSA) are analogues of DMSA with protected thiol groups ("prodrugs"), and DMDMS, DEDMS, DnPDMS, and DiPDMS are various di-esters of DMSA with methyl, ethyl, n-propyl, and isopropyl alcohols, respectively. Thirty minutes after s.c. injection of an LD80 of arsenic trioxide (65 mumol/kg) male NMRI mice were treated with a single equimolar dose (0.7 mmol/kg) of DMSA i.p. or one of the analogues i.p. or via gastric tube (i.g.). Control animals received arsenic trioxide and saline 30 min later. The survival rate was recorded for 30 days. All of the animals treated with DMSA i.p. survived and all controls died within 2 days. Administered i.g., DATSA and DBTSA increased the survival rate to 29% and 43%, and injected i.p. to 86%. Treatment with DMDMS i.p. and i.g., and with DEDMS, DnPDMS, and DiPDMS i.g. did not reduce lethality. Given i.p., DnPDMS increased the survival rate to 72%, and DEDMS and DiPDMS to 86%, respectively. To investigate the efficacy of the DMSA analogues in reducing the tissue content of arsenic, male NMRI mice received an s.c. injection of an LD5 of arsenic trioxide containing a tracer dose of 73-As(III) (42.5 mumol/kg body wt). Thirty minutes later, saline (controls) or a single equimolar dose (0.7 mmol/kg) of DMSA i.p., or one of the analogues i.p. or i.g. was administered. The arsenic content of various organs (blood, liver, kidneys, heart, lungs, spleen, small intestine, large intestine, brain, testes, skeletal muscle, and skin) at 30 min, 2 h, 4 h, 6 h, and 8 h after the arsenic injection was measured using a gamma counter.(ABSTRACT TRUNCATED AT 250 WORDS)
The efficacy of DL-dimercaptopropanol (British Anti-Lewisite, BAL), DL-dimercaptopropanesulfonate (DMPS), and meso-dimercaptosuccinic acid (DMSA) was compared in reducing the acute As2O3 toxicity in mice. Mice were treated with a single equimolar dose of a dithiol compound (0.7 mmol/kg i.p.) 0.5 or 30 min after the s.c. injection of various doses of As2O3. Both DMPS and DMSA were significantly (p less than or equal to 0.05) more effective in mice treated 0.5 min after the poisoning if compared to BAL on an equimolar level. The highest potency ratio (PR) (LD50 with treatment/LD50 without treatment) was found in animals injected with DMSA (PR = 8.6). The corresponding value for DMPS was 4.2, and for BAL 2.1, respectively. In animals treated 30 min after poisoning the efficacy of DMPS (PR = 2.6) was similar to the efficacy of DMSA 2.4, both being only slightly superior to BAL 2.0. DMPS and DMSA were found to be much less toxic than BAL. The LD50 of arsenic was 0.057 mmol/kg. The efficacy of BAL, DMPS, and DMSA in reducing the tissue content of arsenic following acute As2O3 poisoning was investigated in mice (n = 6/group) and guinea pigs (n = 3-4/group). The animals were injected s.c. with 0.043 mmol/kg As2O3 (containing a tracer dose of 74As(III)). Thirty minutes later the antidotes were administered i.p. (0.7 mmol/kg). From 2 to 4 h after As2O3 poisoning bile was collected from guinea pigs. Four h after As2O3 injection the content of 74As in blood, liver, kidneys, spleen, heart, lungs, brain, testes, skeletal muscle, and skin in mice and guinea pigs was measured.(ABSTRACT TRUNCATED AT 250 WORDS)
The protective effects of various chelating agents such as D-penicillamine (D-PEN), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropane sulphonate (DMPS), and N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine), on the renal damage induced by gold sodium thiomalate (AuTM) in rats were studied. Rats were injected i.v. with AuTM at doses of 0.026, 0.066, 0.132, and 0.198 mmol/kg. Urinary excretion of protein, aspartate aminotransferase (AST), and glucose in rats injected with AuTM significantly increased compared to the control levels within 1 day after the injection and thereafter decreased nearly to the control levels at 3 or 7 days. Gold was excreted rapidly during the first day after AuTM injection and excreted gradually thereafter. The concentrations of gold in the kidney and liver at 1 or 7 days after AuTM administration were approximately dose dependent. Treatment with D-PEN, DMSA, DMPS, and bucillamine (1.2 mmol/kg) significantly prevented increases in the urinary excretion of protein, AST, and glucose and the BUN level after AuTM (0.026 mmol/kg) injection. The injection of the chelating agents after AuTM administration showed that D-PEN, DMSA, and DMPS enhanced mainly the urinary excretion of gold and that bucillamine enhanced mainly the fecal excretion of the metal. These chelating agents significantly decreased the gold concentrations in the kidney and liver. The findings suggest that the chelating agents tested can ameliorate the renal damage induced by AuTM.
The heavy metal antidotes sodium-2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) were investigated in anaesthetized dogs for their effects on a variety of physiological variables and parameters. In addition, the influence of both dithiols on oxygen consumption and ferrihaemoglobin production was studied in blood and red blood cells in vitro. DMPS (15 and 75 mg/kg i.v.) did not affect respiration, central venous pressure, left ventricular pressure or cardiac output and showed only marginal, statistically non-significant effects on aortic and effective perfusion pressure. In contrast to the slight, non-significant changes due to DMPS (15 mg/kg i.v.), an equimolar dose of DMSA (12 mg/kg i.v.) led to a slight transient decrease in femoral blood pressure with strong reflex tachycardia and increase in blood flow. The higher DMPS dose (75 mg/kg i.v.), however, caused marked decreases in femoral blood pressure and blood flow, strong changes in blood gases and pH, and lactacidosis. Most of the physiological variables and parameters did not return to the initial level by 60 min. The R-spike of the electrocardiogram decreased, and the T-wave increased. Experiments on the denervated hind leg indicate that DMPS may be a direct vasodilator. The fall of blood pressure due to DMPS was markedly reduced when 30% ferrihaemoglobin had been formed by 4-dimethylaminophenol.HCl (DMAP). The highest DMPS dose (150 mg/kg i.v.) provoked circulatory failure and respiratory arrest. Artificial ventilation with room air restored spontaneous respiration, but one of three animals did not survive this dose for more than 90 min. DMPS and DMSA reacted with oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
24 children with symptomatic urinary tract infection (UTI) underwent systematically ultrasound studies (US) and 99mTc-DMSA renal scans. Among the 15 patients considered as acute pyelonephritis (APN) on clinical grounds, the scan was abnormal in 12 cases, in contrast with only 1 abnormal scan in the clinical subgroup of the lower UTI. Among the 10 abnormal scans that were repeated later on, 6 did completely normalize. US showed only once a parenchymal appearance suggestive for APN. Our findings suggest that the DMSA scan has to be considered at present as the most sensitive imaging technique for the detection of APN.
A set of criteria was developed to standardize assessment of DMSA renal scintigraphy which were performed to evaluate children for acute pyelonephritis and renal scarring. This study was undertaken to assess intra- and interobserver variability in the interpretation of DMSA renal scintigraphy using these criteria. Renal contours and parenchyma were assessed in three zones. Contours were assessed as normal or abnormal and parenchymal defects were evaluated in terms of character, shape and degree in three regions (upper and lower pole and midzone). Two nuclear medicine physicians blindly reviewed 57 DMSA scintigraphy on two occasions each. Disagreement of each observer's evaluation of the same scintigraphy on two different occasions was described as intraobserver variability, and the comparison between readings by each of the two observers was described as interobserver variability. High levels of intra- (95.9% and 90.6% respectively, p < 0.05) and interobserver agreement (84.4%, p < 0.05) were demonstrated. There were minor differences in inconsistencies between the two kidneys or different kidney zones. We conclude that standardization of criteria resulted in higher intra- and interobserver consistency in interpretation of DMSA scintigraphy.
Renal sonography detects abnormality in only 40% of pediatric pyelonephritis. In eight patients shown to have acute pyelonephritis by 99mTc DMSA renal cortical scintigraphy, five were found to have focal abnormalities of renal perfusion by color Doppler sonography in the same sites as the scintigraphic defects (sensitivity-63%). Two of the five patients had normal plain sonograms. False positive studies occurred in patients with documented chronic renal scarring. The specificity of vascular asymmetry was 70%. This preliminary report suggests that, particularly in the patient without pre-existing renal scarring, color Doppler evaluation of the renal vasculature may increase the sensitivity of sonography in the diagnosis of pyelonephritis in children.
The relationship between urine interleukin-6 (IL-6) and interleukin-8 (IL-8)/creatinine quotients and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy, performed within 10 days of acute first-time pyelonephritis and after 1 year, was studied in 41 children. The urine IL-6 and IL-8/creatinine quotients were also related to the urine N-acetyl-beta-D-glucosaminidase (NAG) and albumin/creatinine quotients. Presence of DMSA uptake defects, reflecting local inflammation, in children in the acute phase of pyelonephritis, were associated with elevated urine IL-6/creatinine quotients (median 27 pg/mumol); in children without DMSA changes there was no increase in quotients (median non-detectable) (P < 0.05). Persistent DMSA changes at the 1-year follow-up, probably reflecting renal scarring, were only seen in children with increased urine IL-6/creatinine quotients in the acute phase (P < 0.01). No correlation was found between urine IL-8 and DMSA uptake defects. Vesicoureteral reflux (VUR) at 6-8 weeks did not correlate with the urine cytokine levels in the acute phase. The urine excretion of NAG and albumin, reflecting renal dysfunction, was associated with values of both urine IL-6 and IL-8/creatinine quotients, but not with DMSA defects or VUR. Thus, the initial urine IL-6/creatinine quotients might be used as an indicator of risk for persistent renal damage in acute pyelonephritis.
Infantile renal dysplasias, including multicystic dysplastic kidneys (MCDK), are reported rarely to accumulate radiopharmaceuticals on renal scintigraphy. 99mTc DMSA is a highly sensitive tracer for detecting functioning renal cortical tissue and may be more suited to studying renal dysplasia than 99mTc DTPA. We reviewed the ultrasound studies and 99mTc DMSA scintigrams of 42 infants (age range 1-12 months) with known or suspected MCDK. Overall, uptake on 99mTc DMSA scintigraphy was evident in 6/41 (15%) dysplastic kidneys. Of the 18 patients who underwent nephrectomy, histopathological examination revealed that uptake correlated closely with the presence of mature renal cortical tissue in the affected kidney. Our study shows that a small, but significant number of MCDK will show low-grade uptake on DMSA scintigraphy. This finding may be relevant given the reliance placed on renal scintigraphy in planning treatment for infants with suspected MCDK, particularly with the increasing trend for the non-operative management of this condition.
The relative effectiveness of British Anti-Lewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA), and a new metal binding agent 2,3-bis(acetylthio)propanesulfonamide (BAPSA) was compared by determining their effect on pyruvate metabolism in perfused livers of guinea pigs after repeated treatment with As2O3. Guinea pigs received As2O3, 2.5 mg/kg s.c. twice daily on 5 consecutive days (total dose 25 mg/kg). Sixteen hours after the last dose the livers were perfused (2.5 ml/min/g liver) with Krebs-Henseleit buffer and glucose (10 mmol/l) as substrate for 80 min. After 50 min of perfusion 0.1 or 0.7 mmol/l BAL, DMPS, DMSA, or BAPSA were added to the perfusate for 30 min. Samples of the effluent were collected every 10 min; lactate and pyruvate were determined enzymatically. As compared to controls, a significant decrease in the pyruvate and lactate efflux was observed in perfused livers of guinea pigs treated with As2O3. After influx of BAL (0.1 mmol/l), DMSA (0.7 mmol/l), and BAPSA (0.1 and 0.7 mmol/l) respectively, the pyruvate and lactate efflux and the oxygen consumption (exception BAL 0.1 mmol/l) increased and reached control values without arsenic treatment. On the other hand, the pyruvate and lactate efflux and the oxygen consumption was further significantly decreased after influx of 0.7 mmol/l BAL.
The use of 99mTechnetium dimercaptosuccinic acid (99mTc DMSA) scanning for the early diagnosis of upper urinary tract infections has been preferred for a few years. In this research we investigated the use of 99mTc DMSA scanning in the localization of renal parenchymal involvement in urinary tract infection. Twenty-four children presenting with first acute urinary tract infection were studied. Investigations included physical examination, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antibody-coated bacteria (ACB) and early 99mTc DMSA scanning. 99mTc DMSA scanning was taken as the gold standard method in determining renal parenchymal inflammation. According to the 99mTc DMSA scanning the sensitivity of clinical findings was 57.14%, WBC 23.80%, ESR 33.33%, CRP 14.28% and ACB 71.42% in the localization of urinary tract infection. We propose early 99mTc DMSA scanning performed around the time of infection as a good technique for localization of the level of infection in the urinary tract.
This prospective study was designed to investigate the most relevant radiological approach for the evaluation of urinary tract infections (UTI) in childhood. In the first 48 hours following the diagnosis of UTI, all patients underwent 99mTc dimercaptosuccinic acid (DMSA) scanning, ultrasonography (US) and intravenous urography (IVU). For the imaging of renal parenchymal infection the sensitivity of IVU and US as compared to DMSA scanning were found to be 9.09% and 25%, respectively. It was concluded that 99mTc DMSA, where available, should be the first step for the accurate diagnosis and follow-up of patients with UTI.
Schistosomiasis is among the top five diseases in the world in terms of morbidity, affecting perhaps 200 million people in tropical and subtropical countries. Antischistosomal drugs are toxic and rapidly metabolized. Hence, they must be given in a number of spaced doses. In spite of this there are severe side effects leading to poor patient compliance. This is an ideal situation for the application of sustained drug release to avoid the toxic peak concentration of drug. This study was carried out using Astiban acid, an antimonial drug that is effective against S. mansoni. Unfortunately, the drug is sufficiently soluble that 50 mg will dissolve in 100 mL water in less than a minute. To permit sustained release of intramuscularly injected drug, microcapsules of astiban acid in poly(d,l-lactic acid) were formed by coacervation. Release studies show that an appreciable fraction of the drug is available at the surface for rapid solution. After this surface drug dissolves, the remaining drug is released slowly with half-times of many hours. After the initial burst, the release of drug follows Higuchi's equation up to approximately 80% release, with exponentially decreasing release rates thereafter.