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At least 163 records · Page 9Linked to original sources

Preparation and clinical evaluation of technetium-99m dimercaptosuccinic acid for tumour scintigraphy.

We describe a simple method of pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] preparation for the imaging of medullary carcinoma of the thyroid using commercially available kits. 99mTc(V)-DMSA is available at high pH (approximately 7.5) by adding NaHCO3 solution in the presence of a small amount of reducing agent (SnCl2). On the other hand, trivalent 99mTc-DMSA [99mTc(III)-DMSA] can be obtained at low pH (below 3) in the presence of an excess amount of reducing agent. In the clinical evaluation of a patient with a medullary carcinoma of the thyroid, only 99mTc(V)-DMSA revealed an area of intense accumulation.

3-Iodobenzylguanidine↗

Preoperative scintigraphic evaluation of the location of juxtaglomerular cell tumor.

Juxtaglomerular cell tumor is a rare condition which cannot be correctly diagnosed preoperatively. In the only previously reported case in which scintigraphy has been used, this method failed to detect the tumor. We present a case of juxtaglomerular cell tumor in which renal scintigraphy revealed a well-defined cold area in the hilar region of the left kidney.

Adolescent↗

In vivo estimation of renal volume using a rotating gamma camera for 99mTc-dimercaptosuccinic acid renal imaging.

The in vivo renal volume was determined using SPECT for 99mTc -DMSA renal imaging. The total renal volume was derived by summing the DMSA distribution volumes of the transaxial slices in the whole kidney. In 20 healthy subjects the renal volume in the right kidney was 220 ml for men and 195.2 ml for women, while that in the left kidney was 213 ml for men and 193.7 ml for women. Differences in those values were not statistically significant. A good correlation was found between renal volumes in both kidneys and body surface area. In 106 kidneys including solitary and pathological kidneys, individual renal volume correlated well with individual DMSA renal uptake rate which demonstrates cortical functioning mass, depending on the cortical blood flow. Thus, SPECT enables an accurate noninvasive means of estimating in vivo functioning renal volume.

Adult↗

Estimates of kidney volume by single photon emission tomography: a preliminary report.

Algorithms for the estimation of organ volumes have been developed which may provide whole organ volumes and which may or may not, at the operator's choice, take into account any voids which may be contained within the organ. These algorithms have been applied to the estimation of the volume of the kidneys, in normal subjects and in patients with renal disease. The dimensions of the kidneys were similar to those derived from ultrasound study measurements which were performed independently. Kidney volume should prove especially useful in the diagnosis of early graft rejection and in the diagnosis of glomerulonephritis.

Female↗

The effect of radiopharmaceutical choice on the assessment of the relative renal function in upper urinary tract obstruction.

The relative function of the obstructed kidney (RFOK) was assessed in 43 adult patients with upper urinary tract obstruction (UUTO) using 99mTc-DTPA and 131I-ortho-iodohippurate (OIH) dynamic studies and 99mTc-DMSA dynamic and static studies. The patients were divided into five groups according to the duration and degree of obstruction. Findings were as follows: a) in patients with the first occurrence of acute severe obstruction (group 1), the relative glomerular filtration rate (GFR) was significantly less than the relative effective renal plasma flow (ERPF); b) in patients with chronic severe obstruction and long term uroinfection, the relative ERPF decreased significantly compared with the relative GFR; c) the RFOK calculated from the DMSA dynamic study was the same as both the relative GFR or ERPF in any group; d) the RFOK calculated from the DMSA static study seemed to parallel the relative ERPF more closely than the relative GFR, but in group one it was significantly higher than any of three other estimates. It is concluded that 99mTc-DTPA is the radiopharmaceutical of choice in obstructive uronephropathy, but when interpreting the RFOK, the time course and severity of obstruction, the presence or absence of uroinfection should also be considered.

Adult↗

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. IV. Interaction of 99mTc-DMS and 99Tc-DMS complexes with blood serum proteins.

As a crucial step towards understanding the mechanism of localisation of radiopharmaceuticals in specific target organs, the interaction of the radiopharmaceuticals 99mTc-DMS and 99Tc-DMS with blood serum proteins was studied. The interaction of 99mTc-DMS radiopharmaceutical was examined from two aspects: total protein binding as well as specificity of binding to certain classes of proteins. After in vitro labelling of human sera with 99mTc-DMS, the following values of bound radioactivity to total serum proteins were determined: 65% +/- 3.2% by gel-filtration chromatography; 72% +/- 4.6% by dialysis; while on the basis of precipitation by perchloric and trichloroacetic acid 72.7% +/- 6.8% and 71% +/- 2.3%, respectively. Distribution of 99mTc-DMS or 99Tc-DMS among serum proteins was analysed by agarose gel electrophoresis of the sera at pH 8.6 after in vivo and in vitro labelling of human sera with 99m-Tc-DMS, while the same analysis was performed with 99Tc-DMS complex after in vitro labelling of human and rat sera as well as after in vivo application to the rats. The results obtained demonstrate that carrier serum proteins investigated by agarose gel electrophoresis were in the migration zone of alpha 2-, alpha 1- and beta 1-globulins, whereas the radioactivity found in the serum albumin zone was negligible. Interaction of both Tc-DMS complexes with proteins was very similar, and this conclusion was in good correlation with our previously obtained results in investigations concerning the biochemical behaviour of these complexes.

Alpha-Globulins↗

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. I. Subcellular localization of 99mTc-DMS complex in the rat kidney in vivo.

Subcellular distribution of 99mTc-DMS (dimercaptosuccinic acid) complex in the rat kidney has been studied. One hour after IV injection of labelled DMS preparation kidney tissue homogenate was subjected to differential subfractionation to obtain cell organelles. Radioactivity distribution in relation to total radioactivity of kidney homogenate obtained in five repeated experiments was as follows (+/- SD): nuclei 4.56% (+/- 0.7); mitochondria 5.97% (+/- 0.7); microsomes 3.63% (+/- 0.8) and cytosol 30.92% (+/- 1.8). Specific activities expressed as counts/min/mg of protein were 148,520 (+/- 15%), 97,440 (+/- 17.7%) and 76,180 (+/- 29%) for mitochondria, cytosol and microsomes respectively. Specific activity of the nuclei was 230.060 (+/- 27%) counts/min/mg of DNA. These results show without doubt that this renal imaging agent, successfully used in human medicine, penetrates into kidney cells where it binds mostly to soluble cytoplasmic proteins and mitochondria and to a lesser extent, to both microsomes and nuclei.

Animals↗

Low renal uptake of 99mTc-DMSA in patients with proximal tubular dysfunction.

In nine patients with different types of proximal tubulopathy and a nearly normal glomerular filtration rate a low uptake of 99mTc-DMSA in kidneys was found. The underlying mechanism seems to be an increased urinary excretion of 99mTc-DMSA. This radiopharmaceutical might be used as a marker of proximal tubular dysfunction.

Adolescent↗

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. II. Subcellular localization of 99Tc-DMS complex in the rat kidney in vivo.

In order to extend and confirm our previous studies of in vivo behaviour of 99mTc-DMS in rat kidney cells, the intracellular localization of 99Tc-DMS complex in rat kidney tissue was examined. Animals were injected IV with 99Tc-DMS solution (37 kbq in 1.0 ml) 2 h before killing. Dissected kidneys were homogenized and submitted to differential centrifugation to obtain organelles. The following radioactivity distribution in relation to the total radioactivity of homogenate was obtained in nine experiments: nuclei 3.30% (+/-1.27), mitochondria 9.48% (+/-2.17), microsomes 7.03% (+/-2.34) and cytosol 57.45% (+/-8.01). The subcellular distribution pattern of 99Tc-DMS was in very good agreement with the pattern of 99Tc-DMS binding to kidney cell organelles obtained by the same procedure. Soluble cytoplasmic proteins binding 99Tc-DMS were excluded from a Sephadex G-25 column with the void volume. Their electrophoretic mobility after agarose gel electrophoresis corresponded to beta-lc- and alpha-2-macroglobulins. The results obtained show unambiguously that the investigated complex penetrates into the kidney cells where it binds mostly to soluble cytoplasmic proteins and mitochondria, and to a lesser extent to both microsomes and nuclei. In another series of six experiments, isolated kidney cortical tissue was used, the same procedure was repeated and similar results were obtained.

Animals↗

Biochemical studies of the renal radiopharmaceutical compound dimercaptosuccinate. III. Subcellular distribution and interaction of 99Tc-DMS complex with macromolecules in rat kidney homogenates in vitro.

Rat kidney tissue homogenates, incubated in vitro with 99Tc-DMS were subjected to differential centrifugation. Specific radioactivities of subcellular fractions were as follows: cytosol 13,552, microsomes 3,600, mitochondria, 2,707 cpm/mg protein, and nuclei, 2,642 cpm/mg DNA. The cytosol fraction was further analyzed by ion-exchange chromatography on DEAE-Sephadex A-25 column. In this way it was separated into several distinct protein zones, three of them bearing a significant amount of 99Tc-DMS preparation. The highest specific radioactivities of proteins were eluted from the DEAE-Sephadex column with 30 mmol/l and 50-110 mmol/l NaCl solution. Total nucleic acids isolated from purified nuclei, mitochondria and microsomes contained a certain amount of bound 99Tc-DMS complex. Nuclear nucleic acids had the highest specific radioactivity, suggesting that 99Tc-DMS complex penetrates into the nuclei.

Animals↗

Reversible diminished renal 99mTc-DMSA uptake during converting-enzyme inhibition in a patient with renal artery stenosis.

A patient is described who had accelerated hypertension and unilateral renal artery stenosis, and who developed further deterioration in renal function during treatment with captopril, an angiotension-I (AI) converting-enzyme inhibitor. 99mTc-DMSA uptake was greatly diminished in the stenotic kidney, although renal blood flow and handling of 131I-hippurate was preserved. Uptake of 99mTc-DMSA in the affected kidney returned after substitution of captopril by the vasodilator minoxidil, while a comparable degree of blood pressure control was maintained. Thus, caution must be taken when interpreting results of 99mTc-DMSA scintigraphy in patients with proven or suspected renal artery stenosis treated with an AI converting-enzyme inhibiting drug. Moreover, our finding points to the importance of glomerular filtration in the renal handling of 99mTc-DMSA.

Angiotensin-Converting Enzyme Inhibitors↗

Clinical evaluation of 99mTc(V)-dimercapto succinic acid (DMSA) for imaging medullary carcinoma of thyroid and its metastasis.

99mTc(V)-DMSA kits developed by the Radiopharmaceutical Division, Bhabha Atomic Research Centre, have been evaluated for potential use in scanning medullary carcinoma of the thyroid and its metastases. There were 15 patients with proved medullary carcinoma and 6 patients with other differentiated thyroid carcinoma. Amongst the 15 patients with medullary carcinoma, 12 (80%) showed positive localisation either in the primary or one or more metastatic sites. None of the six patients with carcinoma other than medullary showed increased concentration of 99mTc(V)-DMSA. Of the 37 known metastatic sites in 15 patients with medullary carcinoma, 24 showed concentration of 99mTc(V)-DMSA (64.9%). In addition, 99mTc(V)-DMSA concentration was seen in 14 sites where no evidence of metastasis was revealed. The incidence of 99mTc(V)-DMSA concentration in soft tissue and bone metastasis was similar.

Adult↗

The effects of dimercaptosuccinic acid and other chelating agents on the retention of platinum in the rat kidney after treatment with cisplatin.

The ability of three chelating agents, dimercaptopropanesulphonate (DMPS), dimercaptosuccinic acid (DMSA), and diethylenetriaminepentaacetic acid (DPTA), to reduce the retention of platinum in the kidneys was tested in male Sprague-Dawley rats treated 24 h previously with Cisplatin. DMPS and DMSA, when given as four daily doses of 1 mMol/kg, increased the urinary excretion from 10.1% +/- 1.2% to 13.6% +/- 1.3% and 13.5% +/- 2.6%, respectively, but only DMSA caused a small but significant reduction in the kidney platinum content. DTPA was totally ineffective. It is concluded that none of these agents is likely to be useful for the reduction of Cisplatin-induced renal toxicity in the clinical situation.

Animals↗

Preparation and evaluation of 99mTc(V)-DMSA complex: studies in medullary carcinoma of thyroid.

Consequent to the promising results reported with 99mTc(V)-DMSA for imaging certain types of soft tissue tumors, we have developed methods to prepare this radiopharmaceutical in three ways: from freshly prepared reagents, through the use of a two component kit and use of the standard renal DMSA kit by a modified recipe. The 99mTc(V)-DMSA complex has been subjected to paper electrophoretic and chromatographic procedures and also biodistribution studies. The distinctly different behaviour of this new product compared to that of the well known renal DMSA complex has been clearly established. Scintiimaging in a preliminary clinical trial in patients with medullary carcinoma of the thyroid has been encouraging.

Carcinoma↗

Technetium-99m dimercaptosuccinic acid and ifosfamide tubular dysfunction in children with cancer.

Quantitative 99mTc-dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy was used to asses ifosfamide-induced changes in renal function in 11 children who received chemotherapy for various malignancies. Serial measurements of absolute 99mTc-DMSA renal uptake, calculated on conjugated views, were performed during and after chemotherapy. Data of 37 studies obtained before and at different cumulative dose levels of ifosfamide were analysed in relation to clinical and biochemical parameters. A highly significant relationship between 99mTc-DMSA uptake and cumulative ifosfamide dose was found (P < 0.001). The most frequently observed abnormal pattern on scintigraphic images was decreased kidney uptake together with increased accumulation in bladder. 99mTc-DMSA uptake was more consistent than beta 2-microglobulin values in urine and more sensitive than quantitative hyperaminoaciduria and tubular resorption of phosphate for the detection of ifosfamide-induced tubular dysfunction. 99mTc-DMSA uptake was decreased in both patients with and patients without clinical toxicity. Persistently reduced 99mTc-DMSA uptake was observed in four patients during follow-up; in one of them, who was asymptomatic after ifosfamide therapy, sudden onset of Fanconi syndrome was observed when he was retreated with carboplatin 1 year later. It is concluded that 99mTc-DMSA renal scintigraphy is a suitable method to assess progressive ifosfamide-induced tubular injury whereas scintigraphic imaging is helpful for interpreting renal uptake changes. The test is able to detect subclinical injury and may potentially predict high risk at retreatment.

Antineoplastic Combined Chemotherapy Protocols↗