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Successful imaging of human cancer with indium-111-labeled phospholipid vesicles.

Twenty-four patients with proven primary and/or metastatic cancer received single intravenous injections of phospholipid vesicles containing 0.5 mCi of Indium-111. Gamma camera scintigraphy 1 to 72 hours later visualized tumors in 22 patients (92%), including carcinomas of breast, lung, colon, prostate, kidney, cervix, thyroid, and soft tissue sarcoma, lymphoma, and melanoma. Tumor sites that were identified included soft tissues, bone, lung, liver, lymph node, and spinal cord. There were only two false-positive images in metastatic sites and four false-negative images in metastatic sites. Overall sensitivity for tumors in 97 individual sites was 85%, whereas specificity was 96%. Unsuspected areas of malignancy were seen in the lumbar subdural space, pleura, liver, thyroid, and lung. Besides tumor accumulations, homogeneous uptake was observed in normal liver and spleen. Radiation doses to these two organs were 2.2 and 2.9 cGy/0.5 mCi In-111, respectively. Whole body radiation dose was 0.3 cGy/0.5 mCi. The use of Indium-111-labeled vesicles permits a wide variety of human tumors in primary and metastatic sites to be imaged without toxicity and with radiation doses comparable to other radionuclide scanning techniques.

Humans↗

Kinetics of indium-111-labeled leukemic cells in patients with acute nonlymphocytic leukemia.

The distribution within the body of autologous leukemic cells labeled with indium-111 oxine was studied in seven patients with acute nonlymphocytic leukemia. The leukemic blood cells initially entered the spleen and liver, and the major site of localization was the former rather than the latter. The majority of the leukemic cells had not left the spleen and liver within 48 hr. Liver radioactivity fell transitorily up to the third hr after the initial rise. The clearance curve of radioactivity from the blood showed a plateau or the appearance of a "hump" from 1 to 5 hr after injection of labeled leukemic cells. These results might reflect recirculation of a portion of the leukemic cells between these organs and the bloodstream. In a patient with acute monoblastic leukemia. OKM1 monoclonal-antibody-treated monoblasts showed the lowest recovery into the blood and a greater increase of liver than splenic radioactivity at 30 min after injection. These results suggest the removal of damaged cells by the cytotoxic effects of antibody mediated by reticuloendothelial clearance mainly of the liver and others. In one patient with acute promyelocytic leukemia, leukemic cells accumulated in both kidneys, indicating the possible infiltration of these cells. Since indium-111 oxine stays firmly attached to the cells in spite of the possibility of radiation damaged in a long-term survey, it seems an ideal label for studying leukemic cell kinetics.

Acute Disease↗

111-Indium platelets in monitoring pancreatic allografts in man.

A technique for monitoring pancreatic allografts in man is presented. The method utilizes 111-indium labelled autologous platelets and provides quantitative and qualitative analysis of uptake of the tracer by the graft. Five patients without any significant accumulation of radiolabelled platelets in their transplants had an uneventful recovery and left hospital with satisfactory graft function. The three patients who suffered graft failure showed abnormal uptake of the tracer. This presented as a diffuse platelet accumulation within the transplanted pancreas in the case of acute rejection, or as a focal accumulation in two cases of venous thrombosis. Minor complications such as perigraft haematoma can also be diagnosed using this technique. We suggest that 111-indium labelled platelets provide a valuable diagnostic aid in the management of pancreatic transplant recipients.

Adolescent↗

Endothelial cell labeling with indium-111-oxine as a marker of cell attachment to bioprosthetic surfaces.

Canine vascular endothelium labeled with indium-111-oxine was used as a marker of cell attachment to vascular prosthetic surfaces with complex textures. Primarily cultured and freshly harvested endothelial cells both took up the label rapidly. An average of 72% of a 32 micro Ci labeling dose was taken up by 1.5 X 10(6) cells in 10 min in serum-free medium. Over 95% of freshly labeled cells were viable by trypan blue tests and only 5% of the label was released after 1 h incubations at 37 degrees C. Labeled and unlabeled cells had similar rates of attachment to plastic dishes. Scanning electron microscopic studies showed that labeled cells retained their ability to spread on tissue culture dishes even at low (1%) serum levels. Labeled endothelial cells seeded onto Dacron or expanded polytetrafluoroethylene vascular prostheses by methods used in current surgical models could be identified by autoradiography of microscopic sections of the prostheses, and the efficiency of cell attachment to the prosthesis could be measured by gamma counting. Indium-111 labeling affords a simple and rapid way to measure initial cell attachment to, and distribution on, vascular prosthetic materials. The method could also allow measurement of early cell loss from a flow surface in vivo by using external gamma imaging.

Animals↗

Indium-111 bleomycin tumor scanning in lymphoma.

A new radiopharmaceutical, indium-111 labeled bleomycin (IB), was evaluated as a tumor-imaging agent in 55 patients with lymphoma. Overall disease activity was correctly identified in 79% of 75 whole-body scan obtained 48 hours after intravenous administration of IB. Serial scans in 19 patients accurately reflected changes in their disease status. Lymphatic and soft tissues sites of involvement both above and below the diaphragm were most readily identified by scanning. Bone marrow and hepatic involvements were more difficult to detect because of normal tissue background in the considered organs. Five patients manifested diffuse pulmonary uptake of IB and only in one case was it explained. To determine the accuracy of scanning with IB, we evaluated 731 individual sites of potential tumor involvement with these results: true positives 90%, false negatives 10%, false positives 4%, and true negatives 96%. Thus, tumor scanning with indium-111 bleomycin is an important new technique for the initial staging and serial evaluation of patients with lymphoma.

Adult↗

Synthesis of long indium nitride nanowires with uniform diameters in large quantities.

Large quantities of indium nitride (InN) nanowires are synthesized by the in situ nitriding of indium oxide (In(2)O(3)) powders in an ammonia (NH(3)) flux. Tens of milligrams of nanowires are obtained in one batch. Every 100 mg of In(2)O(3) starting powder can produce up to 65 mg of InN nanowires under the optimized conditions. The synthesized nanowires grow along the [001] direction with excellent crystallinity. They are of high purity and are 30-50 microm in length with an almost uniform diameter of about 100 nm. Photoluminescence measurements of the nanowires exhibit a strong peak at 707 nm. An optical bandgap of about 1.7 eV is estimated based on the absorption spectrum. The experimental results also demonstrate that the approach of nitriding In(2)O(3) powders in situ is feasible for the synthesis of high-purity InN nanowires in large quantities, with good reproducibility and without catalyst materials. The synthesis of InN nanowires in large quantities would be of benefit to the further study and understanding of their intrinsic properties, as well as being advantageous for their potential application in nanodevices.

Indium↗

Metal-induced conformational heterogeneity of transferrins: a spectroscopic study of indium(III) and other metal(III)-substituted transferrins.

The conformation in solution of three different metal(III)-transferrins, namely aluminum(III), gallium(III) and indium(III) transferrin, was investigated by absorption, CD, 1H NMR and 13C NMR spectroscopies. The formation of the respective metal-transferrin complexes and the characteristic 2:1 metal-to-protein binding stoichiometry were unambiguously demonstrated, in all cases, through UV difference studies. The 13C NMR spectra of these metallotransferrins in the carbonyl region are very similar to one another pointing out that the arrangement of the synergistic anion in the binding site must be essentially the same. However, the CD spectra in the near UV (aromatic region) reveal the occurrence of significant differences between indium transferrin, on one side, and the other two derivatives, on the other. Also, the 1H NMR spectra exhibit a number of different features suggesting the occurrence of metal-induced conformational heterogeneity around the metal sites. Such metal-induced conformational heterogeneity probably affects the transferrin-receptor recognition process, resulting in a different metabolic fate of these metals in the organisms.

Carbon Isotopes↗

Pulmonary response of Fischer 344 rats to acute nose-only inhalation of indium trichloride.

We have previously shown that rats dosed intratracheally with indium trichloride (InCl3) develop severe lung damage and fibrosis. However, it is not clear what pulmonary effects would result following accidental occupational exposure to low concentrations of indium by inhalation. The present study uses a model of acute lung injury based on single 1-hr nose-only exposures to 0.2, 2.0, or 20 mg InCl3/m3. Exposure to 0.2 mg InCl3/m3 was capable of initiating an inflammatory response. Seven days following inhalation of 20 mg InCl3/m3 the total cell number, fibronectin, and TNF alpha levels in the bronchial alveolar lavage fluid were 8, 40, and 5 times higher than the control, respectively. Commensurate with the level of lung injury 7 days after exposure, an acute restrictive lung lesion and increased airway responsiveness to acetylcholine were observed. Forty-two days after exposure a compensatory increase in lung volume and carbon monoxide diffusing capacity in the 20 mg InCl3/m3 group suggested recovery from the lung injury. Lung collagen levels were increased in a concentration-dependent manner 42 days postexposure. These data indicate that inhalation of InCl3/m3 causes acute inflammatory changes in the lung.

Administration, Inhalation↗

Testicular toxicity of gallium arsenide, indium arsenide, and arsenic oxide in rats by repetitive intratracheal instillation.

The testicular toxicities of two compound semiconductor materials, gallium arsenide (GaAs) and indium arsenide (InAs), and arsenic oxide (As2O3) were examined in rats by repetitive intratracheal instillation of these substances in suspension twice a week, a total of 16 times. A single instillation dose was 7.7 mg/kg in the GaAs and the InAs groups and 1.3 mg/kg in the As2O3 group. A significant decrease in sperm count and significant increase in the proportion of morphologically abnormal sperm were found in the epididymis in the GaAs group. Especially, abnormal sperm with a straight head increased markedly in this group. In the GaAs-treated rats, there was 40-fold increase in the degenerating late elongated spermatids at the postspermiation stages, stages IX, XI, and XI. From these results, it is indicated that GaAs disturbed the spermatid head transformation at the late spermiogenic phases and caused spermiation failure. InAs caused a sperm count decrease in the epididymis, though its testicular toxicity was relatively weak compared with that of GaAs. As2O3, a probable dissolution arsenic product of GaAs and InAs in vivo, did not show any testicular toxicities in this study. It seems likely that, along with arsenics, gallium and indium play a role in the testicular toxicities of GaAs and InAs.

Animals↗

Comparative pulmonary absorption, distribution, and toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride in Sprague-Dawley rats.

Copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CdTe) are novel compounds used in the photovoltaic and semiconductor industries. This study was conducted to characterize the relative toxicities of these compounds and to evaluate the pulmonary absorption and distribution after intratracheal instillation. Female Sprague-Dawley rats were administered a single equimolar dose (70 mM) of CGS (21 mg/kg), CIS (24 mg/kg), CdTe (17 mg/kg), or saline by intratracheal instillation. Bronchoalveolar lavage fluid (BALF) protein, fibronectin, inflammatory cells, lung hydroxyproline, and tissue distribution were measured 1, 3, 7, 14, and 28 days after instillation. Relative lung weights were significantly increased in CIS- and CdTe-treated rats at most time points. Inflammatory lesions in the lungs consisting of an influx of macrophages, lymphocytes, and PMNs were most severe in CdTe-treated rats, intermediate in CIS-treated rats, and minimal in rats receiving CGS. Hyperplasia of alveolar type 2 cells was present in CIS- and CdTe-treated rats and was greatest in CdTe-treated rats. Pulmonary interstitial fibrosis was observed in CdTe-treated rats at all time points. All three compounds caused marked increases in total BALF cell numbers, with the greatest increase observed in CIS-treated rats. BALF protein, fibronectin, and lung hydroxyproline were significantly increased in all treated animals and were highest in CdTe-treated animals. There was no apparent pulmonary absorption or tissue distribution of CGS. Indium levels increased in extrapulmonary tissues of CIS-treated rats, although Cu and Se levels remained unchanged. CdTe was absorbed from the lung to a greater extent than CGS and CIS. Cd and Te levels decreased in the lung and increased in extrapulmonary tissues. Of these compounds CdTe presents the greatest potential health risk because it causes severe pulmonary inflammation and fibrosis and because it is readily absorbed from the lung may potentially cause extrapulmonary toxicity.

Absorption↗

[Indications for scintigraphy with gallium 67 and with indium 111 labelled leukocytes in the diagnosis of postoperative infections in osteo-articular surgery].

A prospective scintigraphic study using Gallium 67 and granulocytes labelled with Indium 111 was carried out in 60 patients who were thought to have infection following orthopaedic operations. Both investigations gave positive results in 11 of the 16 infections observed. The Indium 111 labelled leucocyte scan was more accurate than the Gallium 67 studies in delineating patients who did not have an infection, and appears to be more reliable in the diagnosis of post-operative sepsis.

Adolescent↗

Indium 111 leucocyte scintigraphy in abdominal sepsis. Do the results affect management?

We have studied the clinical utility of indium 111 autologous leucocyte scintigraphy retrospectively in 45 patients presenting with suspected intra-abdominal sepsis. The sensitivity was 95% (21/22) and the specificity was 91% (21/23). Some 34 of the studies (17 positive and 17 negative) were considered helpful in furthering patient management (76%) and 8, unhelpful (18%). In 3, the study results were misleading and led to inappropriate treatment. Indium 111 scintigraphy, whether positive or negative, provides information in patients with suspected intra-abdominal sepsis upon which therapeutic decisions can be based.

Abdomen↗

Granulocyte-specific monoclonal antibody technetium-99m-BW 250/183 and indium-111 oxine-labelled leucocyte scintigraphy in inflammatory bowel disease.

Thirty-three patients suspected of suffering from inflammatory bowel disease were studied. Autologous leucocytes were labelled with indium 111 oxine and re-injected simultaneously with 0.3-0.5 mg of technetium 99m granulocyte-specific monoclonal antibody BW 250/183. Two scans were obtained, the early scan 3-4 h postinjection (p.i.) and the late scan 18-24 h p.i. Using the endoscopy study as standard, the diagnostic accuracy of both agents was determined. Sensitivity, specificity and accuracy of 111In scans was 88.8%, 100.0% and 93.7% at 4 h and 94.7%, 100.0% and 96.9% at 24 h, respectively. Concerning the results using antibodies, the values were 61.1%, 100.0% and 78.1% at 4 h and 78.9%, 92.8% and 84.8% at 24 h, respectively. Segmental analysis showed concordance in 89.3% and 93.3% of the cases at 4 and 24 h, respectively. Though less sensitive and less accurate than scanning employing indium 111 leucocytes, BW 250/183 granulocyte-specific scintigraphy can be used for inflammatory bowel disease diagnosis and localization.

Adult↗

Indium-111-labeled autologous leukocyte scanning in gastrointestinal graft versus host disease (GVHD).

The technique of scanning with indium-111 autologous leukocytes has been used to assess gastrointestinal graft-versus-host disease (GVHD) following allogenic marrow transplantation. In patients with active disease, abdominal scans showed extensive abnormal localization in the bowel, while in those whose disease was quiescent after responding to treatment, scans showed localized ileocecal involvement. Rectal histology showed excellent agreement with scanning in the diagnosis of GVHD, but in three of six cases with active disease underestimated disease severity. Indium-111 leukocyte scanning is a useful noninvasive technique for the diagnosis and assessment of gut GVHD.

Acute Disease↗

Indium scanning in assessment of acute Crohn's disease. A prospective study of sensitivity and correlation with severity of mucosal damage.

The aim of this study was to determine whether the sensitivity of indium-111 (111In) scanning in the assessment of the activity and extent of Crohn's disease correlates with the severity of intestinal lesions as measured by the newly validated Crohn's disease endoscopic index of severity (CDEIS). Nineteen patients with active (CDAI > 200) colonic (N = 11) or ileocolonic (N = 8) Crohn's disease were assessed by colonoscopy and indium scanning. The intestine was divided into five segments in both studies (rectum, sigmoid and left colon, transverse colon, right colon, and ileum). Seventy of the 86 intestinal segments seen at colonoscopy presented macroscopic lesions of Crohn's disease. On third-hour scintigrams 111In uptake was observed in 52 segments, 51 of which were found to be abnormal at colonoscopy. Predictive positive and negative values of scanning with respect to disease extent assessment were equal to 98% and 44%, respectively. Complete agreement between endoscopic and scintigraphic findings was observed in only six of the 19 patients (32%). Segmental endoscopic indexes of severity (SEIS) were significantly (P < 0.001) lower in false negative (7.9 +/- 4.2) (mean +/- SD) than in true positive (18.0 +/- 9.7) segments as defined by scintigraphy. SEIS values above which 111In uptake was constantly observed did not differ in the different disease locations. When compared macroscopically abnormal intestinal segments according to their 111In uptake grade, the corresponding mean SEIS values increased significantly as the grade increased. Scintigraphic activity, as assessed by the fall in splenic activity, was equal to 23 +/- 11% (N = 19).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Early Indium-111 antimyosin scintigraphy for assessment of regional wall motion asynergy on discharge after myocardial infarction.

To assess the relation between early Indium-111 monoclonal antimyosin antibody scintigraphy and degree of regional asynergy on discharge, 38 patients with a first acute myocardial infarct were studied (18 anterior, 20 inferoposterior infarctions). In 21 patients thrombolytic therapy was administered. On the first day of myocardial infarction, 80 MBq Indium-111 Antimyosin was injected. Planar images, anterior, lateral and left anterior oblique, were made 24 hours later. Localized myocardial uptake was present in 37/38 patients, and was evaluated for Count Density Index (count density of infarct zone/left lung count density) in the left anterior oblique images, which displayed the infarct zone well. Regional asynergy on discharge was evaluated by cross-sectional echocardiography and defined mild (hypokinesia) or severe (akinesia or dyskinesia). Count density index was significantly lower in 15 patients with mild asynergy, compared with 22 patients with severe asynergy (1.61 +/- 0.25 vs. 2.42 +/- 0.40, p less than 0.001). This difference was present in both patient groups treated with or without thrombolysis. We conclude that early count density index, reflecting the amount of local necrosis, is highly correlated to the ultimate degree of wall motion impairment.

Antibodies, Monoclonal↗

Indium 111-labeled granulocyte scan in the diagnosis and management of acute inflammatory bowel disease.

The indium 111 granulocyte scan was used to evaluate 39 individuals known to have or suspected of having inflammatory bowel disease. Twenty-three of these individuals had positive scans and 16 had negative scans. Eighty-seven confirmatory studies, which consisted of barium radiography, endoscopy, operative findings, and histopathology, were performed in 37 of these individuals. The remaining two negative scans corroborated only by clinical course, CBC, and erythrocyte sedimentation rate. In addition, 10 follow-up scans were performed in six of the 39 patients to monitor therapy or investigate a change in symptoms. As an anatomic indicator of acute granulocytic infiltration of the intestinal lamina propria and crypts, the authors found that this scan had a 97 percent rate of sensitivity and 100 percent specificity. Specific indications for the use of the indium 111-labeled granulocyte scan are described. For the authors, in general, this test has become a vital adjunct to endoscopy and radiography in the diagnosis and management of patients with symptoms of inflammatory bowel disease.

Acute Disease↗

Detection of a coronary arterial thrombus by indium-111-oxine-labeled platelet scintigraphy.

Coronary arteriography revealed significant left anterior descending coronary artery stenosis in a 72-year-old man with a history of myocardial infarction. Stenting of the stenotic vessel was performed. Twelve hours after stenting the patient complained of chest pain but emergent coronary arteriography did not show sign of any coronary arterial stenosis. Under suspicion of coronary thrombus formation, indium-111-oxine-labeled platelet scintigraphy was performed 5 days after stenting, and revealed accumulation of indium-111-oxine in the area corresponding to the stent implantation site.

Aged↗