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At least 19 recordsLinked to original sources

Tissue distribution and elimination of indium in male Fischer 344 rats following oral and intratracheal administration of indium phosphide.

The use of indium phosphide (InP) in the semiconductor industry has raised concerns about potential occupational exposure. The tissue distribution and elimination of indium were investigated in adult male Fischer 344 rats following either a single or 14 consecutive daily oral doses, or following an intratracheal instillation of InP (10 mg/kg). The concentrations of indium ions in blood, urine, feces, and tissues were quantified either using direct acid digestion followed by electrothermal atomic absorption spectrophotometry (ET-AAS) or using an extraction method with methyltricapryl ammonium ions to remove indium from the matrix followed by ET-AAS. Indium was poorly absorbed from the gastrointestinal tract in both single and multiple oral dose studies. Upon its absorption, indium was relatively evenly distributed among the major organs such as liver, kidney, lung, spleen, and testes. By 96 h after oral dose treatment, less than 0.11% of the dose of indium was recovered from tissues in the single- or multiple-dose experiment. At 96 h, retention of indium in the body was about 0.36% of the dose (except for lung) following intratracheal instillation of InP. Following oral dose administration, the majority of indium was recovered from the gastrointestinal tract and its contents. The high recovery of indium (73% of the dose) in the feces after intratracheal instillation presumably reflects mucociliary clearance and/or biliary excretion of indium. Urinary indium accounted only for 0.08-0.23% of the dose during a 240-h collection period in both single- and multiple-dose studies. It seems that fecal excretion serves as the major route for indium elimination, and this results from poor absorption. Because of the poor absorption of indium following multiple oral doses or intratracheal instillation of InP, it seems unlikely that indium will accumulate in the body following InP exposure.

Administration, Oral↗

Comparison of indium-111 oxinate labelled autologous granulocytes with indium-111 oxinate and indium-111 chloride as abscess scanning agents. An experimental study in an animal model.

Bacterial abscesses were evoked in goats. Imaging of these abscesses was obtained by means of labelling autologous granulocytes with 111In oxinate, reinjection of the cells into the animal, and scintigraphy by gamma camera one day later. Comparable imaging results, however, were obtained after intravenous injection of 111In oxinate or of 111In chloride. The gamma camera images were supported by tissue distribution studies. In the case of administration of 111In oxinate to the goats, the radioactivity accumulated in the cell fraction of the blood to a significant extent. This did not occur in the case of plain 111In chloride. It remained unexplained why such different accumulation in cells did not result in differences in the scintigraphic studies. Blood clearance studies supplied conclusive evidence that the granulocytes stayed in the circulation for several days following labelling with 111In oxinate and reinjection of the cells into the animals.

Abscess↗

Effects of pH on the stability of the indium-113m blood protein complex and the selective binding of indium-113m to transferrin.

Indium-113m (t1/2 = 100 min; gamma-emission of 393 keV) in trace amounts was injected i.v. in rats. Blood was collected by heart puncture 15 min after the injection, and blood plasma was separated by centrifugation. Gel filtration of plasma on Sephadex G-25M equilibrated with glycine/HCl (pH 2.2-3.6), NaHCO3/CO2 (pH 4.0-11.0) glycine/NaOH (pH 8.6-10.6) or sodium acetate/acetic acid (pH 3.0-5.0) was used to separate free indium from indium bound to macromolecular proteins. Determination of radioactivity in eluted fractions showed that more than 85% of the plasma indium was bound to macromolecules at pH values between 5.0 and pH 10.6. However, dissociation of the indium plasma protein complexes occurred at pH values below 5.5, and more than 90% of the indium radioactivity was found in the low molecular weight fraction at pH 2.2. Affinity chromatography using immobilized antibodies to rat transferrin was used to isolate transferrin at pH 7.4 and 5.5. Immunodiffusion and electrophoresis were used to identify the proteins in fractions obtained by affinity chromatography. It was found that the indium-113m activity was correlated with the content of transferrin and that 80%-90% of this activity was found in fractions that had affinity to antitransferrin. These fractions contained transferrin exclusively at pH 7.4, but additional protein fractions of albumin and alpha1-globulin mobility at pH 5.5. At pH 7.4 and 5.5, 10%-20% of the indium activity was detected in molecular fractions that had no affinity to antitransferrin. Immunologic analyses showed that these fractions contained transferrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of unlabeled indium oxine and indium tropolone on the function of isolated human lymphocytes.

The purpose of this study was to compare the effect of indium oxine and indium-tropolone complexes (nonradiolabeled) on the function of isolated human lymphocytes. peripheral lymphocytes were obtained from 15 normal volunteers and incubated with indium oxine or indium tropolone according to the standard techniques currently used when cells are radiolabeled for subsequent in vivo studies. The phytohemagglutinin-induced (PHA) lymphocyte transformation and a more specific lymphocyte functional test (the mixed lymphocyte reaction) were performed following incubation with the indium complexes. The results indicate that PHA transformation is not affected by either indium oxine or indium tropolone, whereas both chelates reduced the mixed lymphocyte reaction. This suggests that these substances have a selective toxic effect only on a functionally distinct lymphocyte subset (i.e., the cytotoxic T cells) and indicates that there is no significant difference between the two indium chelates in terms of their effect on lymphocyte function.

Adult↗

Fecal leukocytosis, indium-111-labelled autologous polymorphonuclear leukocyte abdominal scanning, and quantitative fecal indium-111 excretion in acute gastroenteritis and enteropathogen carriage.

Abdominal scintiscans were performed and three-day fecal indium-111 radioactivity measured, following injection of indium-111-labeled polymorphonuclear leukocytes, in patients with acute gastroenteritis, enteropathogen carriage, exacerbations of chronic inflammatory bowel disease, and patients without gastrointestinal symptoms. The colon was more commonly inflamed than the small intestine in acute gastroenteritis. Fecal indium-111 radioactivity excretion was elevated in gastroenteritis and in chronic inflammatory bowel disease. The magnitude of the intestinal inflammatory response, as measured by fecal indium-111 excretion, is equivalent in acute gastroenteritis caused by a defined enteropathogen and exacerbations of chronic inflammatory bowel disease. All patients with microscopically detected fecal leukocytosis gave positive intestinal scintiscans, whereas negative scans were obtained on patients without fecal leukocytosis. The results of this study suggest that indium-111-labeled polymorphonuclear leukocytes can be used to study pathophysiology of the enteric inflammatory response in acute infectious gastroenteritis.

Adult↗

Subcellular localization of indium-111 in indium-111-labeled platelets.

Human platelets labeled with [111In]oxine have been suggested for use in platelet kinetic studies, thrombus localization, detection of atherosclerotic lesions, and other scintigraphic techniques. To demonstrate the subcellular localization of indium-111 in labeled platelets, we did subcellular fractionation and measured the amount of indium-111 localized in major platelet components. Human platelets were labeled with [111In]oxine and disrupted by nitrogen cavitation. The cellular material was fractionated on sucrose density gradients. When the subcellular fractions were analyzed, more than 70% of the indium-111 was located in the cytoplasmic pool of the platelets. Chromatography on Sephadex G-100 of aliquots of the labeled cytosol material showed that most of the indium-111 was associated with components of approximately 46,000 daltons. This demonstrated that indium-111 in human platelets labeled with [111In]oxine is located predominantly in platelet cytosol and is associated with cytoplasmic components.

Blood Platelets↗

Hydrogen adsorption on the indium-rich indium phosphide (001) surface: a novel way to produce bridging In-H-In bonds.

The indium phosphide (001) surface provides a unique chemical environment for studying the reactivity of hydrogen toward the electron-deficient group IIIA element, indium. Hydrogen adsorption on the In-rich delta(2 x 4) reconstruction produced a neutral, covalently bound bridging indium hydride. Using vibrational spectroscopy and ab initio cluster calculations, two types of bridging hydrides were identified, a (mu-H)In(2) and a (mu-H)(2)In(3) "butterfly-like" structure. These structures were formed owing to the large thermodynamic driving force for adsorption of H atoms on solid-state indium dimers.

Journal Article↗

Metabolism of indium chelates attached to monoclonal antibody: minimal transchelation of indium from benzyl-EDTA chelate in vivo.

The metabolism of radiolabeled antibodies is important for radioimmunoimaging and therapy. The loss of indium-111 (111In) from the chelate can pose problems in imaging and increases the radiation dose to normal tissues. We have evaluated the loss in vivo of 111In from Lym-1-benzyl-EDTA-111In (an antibody conjugated with isothiocyanato-benzyl-EDTA) in normal mice. A monoclonal antibody (CHA 255) that binds to benzyl-EDTA-indium chelates, but not to other forms of indium, was used to measure the percent of 111In remaining in the chelate. Four days after injection, 97.4 +/- 2.2% of the 111In in the liver was still in the benzyl-EDTA chelate, as was 99.4 +/- 0.7% of the 111In in the urine, and 99.1 +/- 0.7% of the 111In in the blood. Studies in vitro indicate that a benzyl-EDTA-111In-antibody-chelate conjugate is more stable in human serum than a benzyl-DTPA-111In conjugate, and that both benzyl-chelate conjugates are much more stable than an unsubstituted DTPA conjugate.

Animals↗

Platelet labelling with indium-hydroxypyridinone and indium-hydroxypyranone complexes.

In order to identify new compounds which label platelets without affecting their function, three classes of metal chelating agents have been compared with oxine for their efficiency of indium-113m platelet labelling and for their short- and long-term effects on platelet function. The 3-hydroxypyridinones (both 2-ones and 4-ones) and 3-hydroxypyranones are bidentate chelators of trivalent metal ions that are neutrally charged in the metal-complexed form and hence gain access to cells readily. The hydroxypyranone ethylmaltol has been compared with the 3-hydroxypyridin-4-one CP94 and to its structurally related lipophilic analogue CP25 as well as with the 3-hydroxypyridin-2-one, CP02. The platelet labelling efficiencies with these ligands were between 75% and 95% of that obtained with oxine, following a 12-min incubation in saline. The optimal concentration for the hydroxypyridin-2-ones and hydroxypyridin-4-ones was approximately 10 microM compared with 100 microM for the hydroxypyranone ethylmaltol and 60 microM for oxine. Oxine and tropolone were found to produce significant inhibition of platelet aggregation to collagen in short-term experiments (10 min) or in longer term (18 and 42 h) ex vivo platelet cultures respectively. By contrast, ethylmaltol had no such inhibitory effects at either time interval. The relatively hydrophilic hydroxypyridin-4-one CP94 showed no inhibitory effects on collagen-induced aggregation in short-term studies, unlike the more lipid-soluble derivative CP25. These results suggest that ethylmaltol and related pyranones may have advantages over oxine and tropolone as indium platelet labelling agents where it is important not to damage platelets by the labelling process itself.

Blood Platelets↗

Indium 111-granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease. A comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion.

Indium 111-leukocyte scanning has recently been introduced as a new method for imaging inflammatory bowel disease. The technique has recently been made more specific for acute inflammation by labeling a pure granulocyte fraction rather than the conventional mixed leukocyte preparation. We now report a prospective study comparing 111In-granulocyte scanning with endoscopy, histology, and fecal 111In-granulocyte excretion for the assessment of disease extent and severity in colonic inflammatory bowel disease. In 52 patients with Crohn's disease or ulcerative colitis, disease extent and severity were assessed macroscopically, histologically, or by scanning using a numerical grading system. Excellent correlations were found between both endoscopy and histology and 111In scans [r = 0.90 (endoscopy) and r = 0.90 (histology) for extent; r = 0.86 and r = 0.91 for disease activity]. Severity graded by scanning also showed a close correlation with fecal 111In-granulocyte excretion (r = 0.90). Indium 111-granulocyte scans are a rapid, accurate, noninvasive means of assessing both disease extent and severity of colonic involvement in inflammatory bowel disease.

Biopsy↗

Chronic toxicity of indium arsenide and indium phosphide to the lungs of hamsters.

Chronic toxicity of indium arsenide (InAs) and indium phosphide (InP) was studied in male Syrian golden hamsters which received InAs or InP particles containing a total dose of 7.5 mg of arsenic or phosphorus by intratracheal instillations once a week for 15 weeks. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During their total life span, the cumulative body weight gain of hamsters in the InAs group was suppressed significantly compared with that in the control group, but not in the InP group when compared with that in the control group. Concerning the histopathological findings of the lung, the incidence rates of proteinosis-like lesions, alveolar or bronchiolar cell hyperplasia, pneumonia, emphysema and metaplastic ossification observed in the InAs or InP group were significantly higher than those observed in the control group. From these results, it would seem that InAs and InP produced severe damage to the lungs of hamsters.

Animals↗

Uptake of indium-111-labeled platelets and indium-111 oxine by murine kidneys after total-body irradiation.

Radiation nephropathy is a well-known late manifestation of renal irradiation in human beings and experimental animals. Its pathogenesis is unclear, but vascular injury may play a role. Endothelial cells have been demonstrated to manifest a variety of abnormalities within hours of exposure to radiation. In the present experiments mice were exposed to lethal doses of whole-body radiation, and the distribution of 111In-labeled platelets was evaluated during the first week after irradiation. The purpose was to determine if early abnormalities of endothelial cells would be manifested by altered sequestration of platelets in kidneys and other organs. It was found that the indium accumulated in the kidneys of irradiated mice to a greater extent than in nonirradiated mice, supporting the possibility of early vascular injury. In control experiments, administration of 111In-oxine was also followed by excessive accumulation of radioactivity in kidneys of irradiated mice, but the pattern of accumulation differed from that seen after injection of radiolabeled platelets. Renal hyperemia was not demonstrable with 51Cr-labeled red cells, renal vascular permeability was not detected with 125I-labeled albumin, and the pattern of renal uptake of plasma proteins labeled with 59Fe or 111In did not coincide with that seen from 111In administered as labeled platelets or oxine. Renal uptake of 111In-oxine was not associated with alterations in urinary or fecal excretion or an increase in total-body retention of the radioisotope. The findings are consistent with the notion that renal vascular injury at the time of irradiation results in accumulation of platelets or platelet constituents during the first week after total-body irradiation of mice.

Animals↗

Dissociation of indium from indium-111-labelled diethylene triamine penta-acetic acid conjugated non-specific polyclonal human immunoglobulin G in inflammatory foci.

Several investigators have reported retention of indium-111 in infectious foci after intravenous injection of 111In-labelled immunoglobulin G (IgG). With this study we intended to test the hypothesis that, upon administration of 111In-diethylene triamine penta-acetic acid (DTPA-IgG), 111In is retained in the infectious foci after dissociation from IgG. Therefore we measured the tissue distribution of double-labelled 111In-DTPA-IgG-(carbon-14) in rats with a focal infection and compared the results with corresponding data for DTPA-IgG-(14C). DTPA-conjugated IgG was labelled with 111In via citrate transchelation. 111In-DTPA-IgG and DTPA-IgG were labelled with 14C through methylation. High-performance liquid chromatography (HPLC) and instant thin-layer chromatography analysis were performed to test the in vitro stability of the labelled proteins. Young Wistar rats with a Staphylococcus aureus infection of the left calf muscle were injected intravenously with 0.2 ml of a solution containing either 0.4 MBq 111In and 30 kBq 14C or 30 kBq 14C labelled to 80 micrograms IgG. Groups of five rats were sacrificed at 2, 6, 24, and 48 h. p.i. Activity uptake was determined for plasma, urine, abscess, muscle and various other tissues. Averages and standard deviations were calculated for groups of five rats. HPLC analysis was performed on plasma and urine samples taken up to 48 h p.i. The radiochemical purity of the IgG preparations was > 95%. The labelled preparations appeared stable in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Abscess↗

In vivo imaging of rat lymphocytes with an indium 111-labelled anti-T cell monoclonal antibody: a comparison with indium 111-labelled lymphocytes.

An indium 111-labelled mouse anti-rat T cell monoclonal antibody, MRC OX-19, was injected intravenously into rats to establish the usefulness of radiolabelled anti-lymphocyte antibodies in imaging lymphoid tissues. Antibody binding in vivo, measured by immunofluorescence analysis of cell suspensions made from lymphoid tissues, was detectable on lymphocytes in blood, spleen and lymph nodes. The extent of binding was time and antibody-dose dependent. Doses of antibody above 80 micrograms/kg body weight resulted in modulation, i.e. loss of CD 5 (T1) molecules from the cell surface, although the cells remained in the circulation. Modulation was demonstrable within 2 h and for at least 24 h after a single injection of antibody. Intravenous injection of 111In-MRC OX-19 resulted in levels of in vivo binding comparable with those seen with unlabelled antibody. Scintillation imaging showed early splenic localisation persisting over 48 h, a more gradual localisation in the lymph nodes seen clearly at 24 h and a steady background. Comparison of the in vivo distribution of labelled antibody and 111In-tropolone-labelled lymphocytes showed that both could be used for external imaging of lymphocytes by scintillation camera.

Animals↗

Comparison of indium-111 nonspecific polyclonal IgG with indium-111-leukocytes in a canine osteomyelitis model.

Osteomyelitis was surgically produced in the proximal tibia of ten dogs. A sham operation was performed on the other tibia. Early (3 hr) and late (20 hr) imaging was performed 1, 4, 7, 10, and 13 wk later, while the osteomyelitis progressed from acute to chronic. Indium-111-IgG had a significantly greater accumulation at the osteomyelitis site than 111In-leukocytes, both during early (p = 0.001) and late (p = 0.03) imaging, and at each of the weeks studied (p less than 0.001). During early imaging, both agents gave equivalent lesion to background ratios. On the late images, the 111In-leukocytes gave significantly higher lesion-to-background ratios than 111In-IgG (p less than 0.001) and higher ratios than they did during the early images (p less than 0.001). Both agents had greater accumulation in acute osteomyelitis than in chronic osteomyelitis (p less than 0.02). Osteomyelitis in the surgical site can be distinguished from the uptake in the sham surgery site using 111In-leukocytes, but not when using 111In-IgG.

Animals↗

Uptake of indium-111 in the liver of mice following administration of indium-111-DTPA-labeled monoclonal antibodies: influence of labeling parameters, physiologic parameters, and antibody dose.

Liver uptake of indium-111 (111In) in mice was investigated following administration of 111In-DTPA murine monoclonal antibodies (111In-DTPA-MAbs) labeled by the cyclic anhydride method. Biodistribution of HPLC-purified 111In-DTPA-MAb preparations was checked with a low (0.2 micrograms) and a high (8.0 micrograms) MAb dose. Using Bio Gel P-30 for desalting the MAb-conjugates, 111In uptake in the liver amounted to 8%-9% of the injected dose (ID) and was independent from the MAb dose, the DTPA-to-MAb molar ratio, tumor growth and biologic variability (different MAbs and different strains of mice). Using Sephadex G-25 for desalting, 0.2 micrograms doses from 7 out of 26 preparations showed increased liver accumulation of 111In in non-tumor mice ranging from 15%-25% of ID. Corresponding high doses led to a "normal" value of 8%-9%. Increased liver uptake of the low dose could not be reduced by coadministration of the unconjugated MAb, but was normal after reinjection of "in vivo filtered" material. An inverse intracellular distribution of 111In activity between sediment and supernatant of liver homogenates, following the administration of the low and the high MAb dose, indicated an artifact of the labeling procedure rather than an inherent biological property of labeled MAbs.

Animals↗

Comparison of leukocytes labeled with indium-111-2-mercaptopyridine-N-oxide and indium-111 oxine for abscess detection.

Indium-111 leukocyte scanning has evolved into a practical and highly accurate method for the identification of infectious and inflammatory processes. The most commonly used agent for labeling leukocytes has been [111In]oxine. We have investigated a newer agent, 2-mercaptopyridine-N-oxide (Merc) at our institution which unlike oxine, allows us to label leukocytes in plasma, using a simple kit procedure. Of the 92 consecutive patients referred for detection or localization of an infectious process, autologous leukocytes of 55 patients were labeled with [111In]Merc, while those of the remaining 37 patients were labeled with [111In]oxine. The sensitivities for Merc and oxine procedures were 87% and 92%, respectively, while the respective specificities were 100% and 92%. We conclude that the [111In]Merc-labeled leukocytes are equally effective as [111In]oxine-labeled leukocytes in detecting infectious processes. The use of [111In]Merc is advantageous over [111In]oxine for white blood cell labeling because of its easier preparation.

Abscess↗