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Indium-111-oxine labeled leukocyte uptake in Ki-1-positive anaplastic large cell lymphoma.

Indium-111-oxine labeled leukocyte ((111)In-WBC) scintigraphy is well known for its ability to localize in areas of active infection, but not in areas of lymphomatous involvement. We present a case of Ki-1-positive anaplastic large-cell lymphoma that was initially thought to be a case of multifocal osteomyelitis because of positive uptake on a (111)In-WBC scan. The areas of abnormal uptake on the indium scan were demonstrated histopathologically to be sites of lymphomatous involvement in bone.

Bone Neoplasms↗

Detection of platelet deposition at the site of peripheral balloon angioplasty using indium-111 platelet scintigraphy.

Restenosis after balloon angioplasty may be mediated through platelet deposition at the site of arterial dilatation. The purpose of this study was to determine whether platelet deposition at the site of dilatation could be detected using indium-111 platelet scintigraphy. Fifteen patients, aged 60 +/- 9 years, with iliac or femoral (n = 12), renal artery (n = 2) or distal aortic (n = 1) stenoses were studied. All patients received intravenous heparin at the time of dilatation. Labeled platelets containing 471 +/- 65 muCi indium-111 were injected 0.25 to 4 hours after dilatation and 1 to 24 hours after imaging. In 11 of 12 patients with iliac and femoral dilatations, focal uptake was demonstrated at the angioplasty site. In 4 patients (2 patients with renal, 1 patient with iliofemoral, and 1 with distal aortic stenoses), uptake at the dilatation sites was not detected. This preliminary study indicates that despite intravenous heparin, platelets accumulate at sites of balloon dilatation. Platelet scintigraphy may be useful in predicting sites of future narrowing after angioplasty and may be used to test the efficacy of antiplatelet therapy in retarding restenosis.

Adult↗

Early image acquisition after administration of indium-111 platelets in clinically suspected deep venous thrombosis.

Indium-111 platelet scintigraphy accurately detects acute deep venous thrombosis in asymptomatic high-risk patients and may be used as a surveillance test. However, its value in symptomatic patients and its accuracy early after platelet injection are not satisfactorily established. The latter is important for timely institution of therapy. Accordingly, 65 patients (67 limbs) with suspected deep venous thrombosis (symptom duration 8 +/- 10 days, mean +/- standard deviation) were prospectively studied with platelet scintigraphy and contrast venography. Platelets were labeled with 405 +/- 101 mCi indium-111 oxine. The labeling efficiency was 80 +/- 10%. All images were acquired within 120 minutes after intravenous administration of the platelet suspension. Both platelet scintigraphy and venography were interpreted independently by 2 blinded observers (for each technique). Five separate analyses were performed. Each scintigraphic reader was compared to each venographic reader. A fifth analysis--consisting of readings with blinded agreement of both readings of the platelet scans and both readings of the venograms--was performed. Interobserver agreement was 92% for venography and 79% for scintigraphy. Excluding anticoagulated patients, the sensitivity of platelet scintigraphy was between 38 and 46% and the specificity was between 92 and 100%. Thus, early imaging of labeled platelets for the diagnosis of symptomatic deep venous thrombosis carries a high specificity but a much lower sensitivity. It is speculated that the low sensitivity is related to the inactivity of the thrombus. This may suggest that early imaging will only be useful in patients whose symptoms are of recent onset.

Blood Platelets↗

Indium-111 labeled leukocytes in the evaluation of suspected abdominal abscesses.

Sixty-eight indium-111-labeled leukocyte imaging studies were performed in 53 patients with suspected abdominal abscesses. Twenty-nine studies gave abnoramal results. Nine wound infections were demonstrated, and 14 abscesses were correctly identified. Four studied demonstrated colonic accumulation, one of which remains unexplained, and two accessory spleens were identified. Indium-111 leukocyte imaging is a sensitive and specific study in evaluating patients with suspected abdominal abscess. Differentiation of abscess from other causes of inflammation has not been a problem. The exact role of leukocyte imaging compared with gallium-67 citrate imaging, ultrasound and computerized tomography remains to be determined.

Abdomen↗

Synthesis of a monoclonal antibody-indium-111-porphyrin conjugate.

Antibodies were labelled with indium-111 with a view to their use in the radio-immunodetection of cancers. The covalent coupling between indium-111 porphyrin and monoclonal antibodies (IgG and F(ab')2 fragment) was achieved using the ester activated method [N-hydroxy-succinimide/1-ethyl-3-(3-dimethylaminopropyl)carbodiimide]. After purification, this provided conjugated with specific activities of 6 muCi/micrograms Mab (9.3 molecules per Mab) or 1 muCi/microgram (F(ab')2 fragment (1.5 molecule per F(ab')2). ELISA procedures suggested the full retention of immunoreactivity by the radiolabelled antibodies.

Animals↗

An evaluation and comparison of the pulpal response to gold foil and indium alloy.

All teeth restored with gold foil had pulpal changes marked by persistent hemorrhage, destruction of odontoblasts, and inflammation. Bacteria were found more frequently on cavity walls of teeth restored with gold foil and with increasing frequency for all materials as the observation period became longer. The presence or absence of bacteria could not be related to the pulpal response for either indium alloy or gold foil. Because this and previous studies indicated that gold foil in direct contact with prepared dentin surfaces produces pulpal injury, a base to protect the pulp is indicated. Indium alloy or another appropriate base could be used for the required pulpal protection.

Animals↗

Prognostic significant of indium-111 antimyosin antibody uptake in patients with dilated and hypertrophic cardiomyopathy.

The prognostic significance of myocardial uptake of indium-111 antimyosin was evaluated in 15 patients with idiopathic cardiomyopathy: 10 patients with dilated cardiomyopathy and 5 patients with hypertrophic cardiomyopathy. Seven of the 10 patients with dilated cardiomyopathy showed positive images; three of these 7 patients with strongly positive scans died within 3 months after scintigraphic examination. Four of the 5 patients with hypertrophic cardiomyopathy showed positive images; two of these patients with dilated left ventricle had prominent positive scans and higher heart to lung ratio. One of these two patients died 12 months after antimyosin scan. The heart to lung ratio of antimyosin uptake in total patients was correlated with left ventricular end-diastolic dimension (r = 0.51, P less than 0.05), end-systolic dimension (r = 0.57, P less than 0.05) and ejection fraction (r = -0.60, P less than 0.05) measured by echocardiography. Although the number of patients is small and the study is preliminary, indium-111 antimyosin antibody imaging could be of value in establishing prognosis of patients with dilated and hypertrophic cardiomyopathy, in selecting patients for cardiac transplantation, and in evaluating the effects of therapeutic interventions.

Adult↗

An optimized antibody-chelator conjugate for imaging of carcinoembryonic antigen with indium-111.

A monoclonal antibody to carcinoembryonic antigen showing minimal cross-reactivity with blood cells and normal tissues was derivatized with benzylisothiocyanate derivatives of EDTA and DTPA. Seven chelators per immunoglobulin could be incorporated without loss of immunoreactivity. The resulting conjugates, labeled with indium-111, showed low liver uptake in animals. A cold kit, comprising the DTPA conjugate at a molarity of antibody bound chelator exceeding 1 x 10(-4) M, gave radiochemical yields of indium labeled antibody of greater than or equal to 95% and was stable for 1 yr.

Animals↗

Synthesis and characterization of dual function vanadyl, gallium and indium curcumin complexes for medicinal applications.

Novel bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione (curcumin) complexes with the formula, ML(3), where M is Ga(III) or In(III), or of the formula, ML(2) where M is [VO](2+), have been synthesized and characterized by mass spectrometry, infrared and absorption spectroscopies, and elemental analysis. A new ligand, bis[4-acetyl-3-hydroxyphenyl]-1,6-heptadiene-3,5-dione (diacetylbisdemethoxycurcumin, DABC) was similarly characterized; an X-ray structure analysis was performed. Vanadyl complexes tested in an acute i.p. testing protocol in STZ-diabetic rats showed a lack of insulin enhancing potential. Vanadyl complexes were, however, more cytotoxic than were the ligands alone in standard MTT (3-[4,5-dimethylthiazole-2-yl]ate, -2,5-diphenyl-tetrazolium bromide) cytotoxicity testing, using mouse lymphoma cells. With the exception of DABC, that was not different from VO(DABC)(2), the complexes were not significantly different from one another, with IC(50) values in the 5-10 microM range. Gallium and indium curcumin complexes had IC(50) values in the same 5-10 microM range; whereas Ga(DAC)(3) and In(DAC)(3) (where DAC=diacetylcurcumin) were much less cytotoxic (IC(50)=20-30 microM). Antioxidant capacity was decreased in VO(DAC)(2), Ga(DAC)(3), and In(DAC)(3), compared to vanadyl, gallium and indium curcumin, corroborating the importance of curcumin's free phenolic OH groups for scavenging oxidants, and correlated with reduced cytotoxic potential.

Animals↗

Indium-111 capromab pendetide (ProstaScint) uptake in neurofibromatosis.

We report on the demonstration of nonspecific accumulation of indium-111 capromab pendetide (ProstaScint) in neurofibromas in a patient with a rising prostate-specific antigen level after prostatectomy. Although the immunoconjugate is targeted to a specific membrane antigen present in human prostate carcinoma, nonspecific uptake can occur in other entities. Indium-111 capromab pendetide scintigraphy is a valuable diagnostic tool that should always be interpreted within the context of the clinical history and the laboratory and radiologic findings to avoid misinterpretation.

Antibodies, Monoclonal↗

The semiconductor elements arsenic and indium induce apoptosis in rat thymocytes.

Indium arsenide and gallium arsenide are important new materials in the semiconductor industry due to their superior electronic properties in comparison with the older silicon-based materials. Animal experiments have shown that exposure to these compounds induces marked alterations in gene expression and immune response. Toxicity to the immune system has frequently been related to T and B cell apoptosis. In the present study we show that the semiconductor elements indium (In) and arsenic (As) are able to induce apoptosis in rat thymocytes in vitro. The results show that exposure to InCl3 (1, 10, or 100 microM) or Na AsO2 (0.01, 0.1, or 1 microM) induced DNA laddering after 6 h of incubation without compromising cell viability. These results were corroborated by flow cytometry analysis of propidium iodide-loaded cells, showing a typical high hypodiploid DNA peak in apoptotic thymocytes. Higher doses of In (1 mM) or As (10-100 microM) induced cell death by necrosis. These data indicate that In and As can induce apoptosis and necrosis in T lymphocytes in a dose-dependent manner, which may be of relevance for their immunotoxicity.

Animals↗

Indium-111 platelet scintigraphy in carotid disease.

Forty-five patients (35 men, 10 women) undergoing carotid surgery had Indium-111 platelet scintigraphy as part of their preoperative work-up. Imaging was performed within three hours after injection of the Indium-111. A second series of views was obtained 24 hours later and repeated at 24 hour intervals for two days. Of 54 scintigrams, 22 were positive and 32 negative. Positive results were defined as a twofold or more increase in local activity on a visualized carotid after 24 hours. The sensitivity of the method was 41%, intraoperatively, and the specificity, 100%. The low sensitivity places this method behind sonography and duplex-scanning for screening patients for surgery. We believe that indications for platelet scintigraphy are limited to: 1. Repeated transient ischemic attacks in the same territory with minimal lesions on arteriography and non-homogeneous plaque on duplex scan; 2. Symptomatic patients being treated medically as a possible argument for surgery; 3. Determining therapeutic policy for patients having experienced a transient ischemic attack with a coexisting intracardiac thrombus.

Aged↗

Spectroscopic gas analyzers based on indium-phosphide, antimonide and lead-salt diode-lasers.

Currently available semiconductor lasers for spectroscopy in the near- and mid-infrared region based on direct band-to-band transitions as gallium-arsenide, indium-phosphide, antimonides and lead-salt containing compounds will be discussed together with the main features of different tunable diode-laser absorption spectrometers for trace gas analysis. Measurements of atmospheric carbon dioxide with a room-temperature 2 microm indium-phosphide laser, applications of antimonide lasers for methane and formaldehyde sensing in the 3-4 microm range and a fast chemical sensor for methane flux measurements based on lead-salt diode-lasers operating near 7.8 microm will be presented.

Antimony↗

Indium as internal standard in square wave anodic stripping analysis of lead in blood with microelectrode arrays.

The toxic effects of lead on humans, especially children have been well documented. ASV has been an important technique in the analysis of lead in blood of humans. This research has demonstrated that indium(III) can be used as an internal standard in the analysis of lead in blood samples with mercury film microelectrode arrays. Indium is a good choice because of a low endogenous blood concentration and because baseline separation of anodic stripping peaks among Cd, In, and Pb can be achieved under appropriate conditions. The concentration of sodium bromide strongly influences the resolution of these metals and the sensitivity of ASV to In(III) in solution. Square wave anodic stripping voltammetry together with screen-printed microelectrode arrays showed that the ratio of the anodic stripping peak currents of Pb and In varies linearly with the concentration of Pb in blood samples ranging from 1.2 to 30.0 micrograms/dL. The average intraassay precision (rsd) was 6.7%.

Electrochemistry↗

New chelating agent for attaching indium-111 to monoclonal antibodies: in vitro and in vivo evaluation.

111In possesses excellent radiophysical properties suitable for use in immunoscintigraphy of cancerous tissues when attached to an antitumor antibody. However, 111In has a tendency to accumulate in normal tissues such as liver. Instability of the linkage between 111In and antibody may contribute to this problem. To avoid this, we developed a new bifunctional chelating agent, 1,3-bis[N-[N-(2-aminoethyl)-2-aminoethyl]-2-aminoacetamido]-2-(4- isothiocyanatobenzyl)propane-N,N,N',N'',N''',N'''',N''''',N'''''- octaacetic acid (LiLo), that forms a kinetically stable chelate with metal ions such as indium. Using LiLo, indium-111 was conjugated to a human monoclonal antibody, 16.88. Competitive binding analysis revealed that the 16.88-LiLo conjugate is as immunoreactive as the unconjugated native antibody. This conjugate was compared with 111In-16.88, where diethylenetriaminepentaacetic acid dianhydride (DTPAa) was used as the chelating agent. In vitro stability studies showed that 111In was more stably bound to 16.88-LiLo than to 16.88-DTPA. Biodistribution studies in athymic mice bearing colorectal tumor xenografts indicated less liver retention with 16.88-LiLo than with 16.88-DTPA. These results demonstrate that LiLo is superior to DTPAa for attachment of 111In to the monoclonal antibodies.

Animals↗

Preliminary study of the metal binding site of an anti-DTPA-indium antibody by equilibrium binding immunoassays and immobilized metal ion affinity chromatography.

Creating metal coordination sites by modifying an existing enzyme or by eliciting antibodies against metal chelate haptens is of great interest in biotechnology to create enzyme catalysts with novel specificities. Here, we investigate the metal binding potential of a monoclonal antibody raised against a DTPA-In(III) hapten (mAb 734). We study its relative binding efficiency to metals of biological relevance by equilibrium binding immunoassays and immobilized metal ion affinity chromatography, two approaches which can give complementary information regarding composition and/or structure of the metal binding site(s). Fe(III), Fe(II), Cu(II), Mg(II), Ca(II), and Zn(II) binding was compared to In(III). All of them were shown to displace indium, but their affinity for mAb 734 decreased by 100-fold compared to indium. Competitive metal binding immunoassays between Zn(II) and In(III) revealed an unusual behavior by Zn(II) which remains to be explained. Moreover, IMAC allowed us to predict the metal binding amino acids involved in the antibody paratope. The antibody metal binding site was shown to contain at least two histidine residues in a cluster, and the presence of aspartic and glutamic acid as well as cysteine residues could not be excluded. Thus, simple competition studies allows us to obtain some partial information on the metal binding structural features of this anti-metal chelate antibody and to guide our screening of its catalytic potential.

Antibodies, Monoclonal↗

Syntheses of functionalized indium porphyrins for monoclonal antibody labeling.

The syntheses and characterizations of five differently hydrosoluble monosubstituted aryl porphyrins are reported. Their metallation with indium-111 was achieved and provided tracers with strong specific activities. The covalent coupling between indium-111 porphyrins and BSA served as a model reaction for the definition of the best experimental coupling conditions; the transposition to the labeling of anti-CEA monoclonal antibody was realized. The conjugates exhibited an in vitro good mAb-labeling efficiency, as well as a good preservation of immunoreactivity.

Animals↗

Two-dimensional indium sulfide framework constructed from pentasupertetrahedral p1 and supertetrahedral t2 clusters.

A new open-framework indium sulfide ([In12S24H2]10-) constructed from pentasupertetrahedral sulfide clusters ([In8S17H],9- P1) and supertetrahedral sulfide clusters ([In4S10H],7-) T2) has been prepared through hydrothermal synthesis. Unlike previously reported P1 clusters that require divalent metal cations, the P1 cluster reported here consists of only trivalent ions (In3+) and is the only known example of tetrahedral clusters with a core sulfur site bonded to four trivalent ions. Each P1 cluster is joined to three T2 clusters (vice versa) to form an infinite two-dimensional sheet stacked along the crystallographic c-axis. In contrast with known three-dimensional open-framework indium sulfides in which locations of extraframework amines are rarely known due to disorder, structure-directing amine molecules are much less disordered as a result of host-guest N-H...S hydrogen bonding. The UV-vis diffuse reflectance spectrum shows that this material is a wide band gap semiconductor.

Crystallography, X-Ray↗