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Acute pulmonary toxicity of copper gallium diselenide, copper indium diselenide, and cadmium telluride intratracheally instilled into rats.

Acute toxicity studies were conducted on copper gallium diselenide (CGS), copper indium diselenide (CIS), and cadmium telluride (CT), three novel compounds used in the photovoltaic and semiconductor industries. Female Sprague-Dawley rats (six rats/dose) were administered 0, 12, 25, 50, or 100 mg/kg body wt of CGS, CIS, or CT by intratracheal instillation. At 72 hr after treatment, body weight gain was significantly decreased in the 100 mg/kg CIS group and in all CT dose groups. Lung weights were increased in most chemical-treated rats, with CT causing the greatest increase. Total numbers of cells in bronchoalveolar lavage fluid (BALF) were significantly increased in treated rats and were greatest in the 100 mg/kg CIS group. Differential cell counts of BALF demonstrated a marked decrease in the percentage of alveolar macrophages and an increase in the percentage of polymorphonuclear leukocytes in all dose groups of all three chemicals. Slight to moderate increases in lactate dehydrogenase activity were observed in BALF from CGS- and CIS-treated rats; marked increases were observed in CT-treated rats. BALF protein was significantly increased in rats treated with CIS and CT. Microscopic examination revealed lymphoid hyperplasia in lungs of rats treated with all three chemicals. CT caused necrosis of the terminal bronchiolar epithelium and epithelium of the alveolar duct region with inflammation, prominent fibrin exudates, and type II cell hyperplasia. CGS and CIS also caused intraalveolar inflammation and type II cell hyperplasia, but did not cause the necrosis and fibrin exudate observed in lungs of CT-treated rats. Based on changes in lung weight, BALF indices, and histopathology, CT was the most toxic for the lung; CIS had intermediate toxicity and CGS was the least toxic. The solubilities of CGS and CIS were relatively low and similar at both pH levels and do not readily explain the observed differences in pulmonary toxicity. The solubility of CdTe was considerably greater than that of CGS and CIS and likely contributed to the greater toxicity of this compound.

Animals↗

Gallium nitrate accelerates partial thickness wound repair and alters keratinocyte integrin expression to favor a motile phenotype.

The nitrate form of the Group III transitional element gallium (GN) increases expression of specific structural components of the provisional wound matrix (i.e., collagen type I, fibronectin) in human dermal fibroblasts. To evaluate the potential of GN as a therapeutic option in management of cutaneous trauma, GN-treated partial thickness porcine wounds and experimentally "injured" human keratinocyte (NHK) monolayer cultures were compared with mirror image control (i.e., saline-treated) sites. GN suppressed cell proliferation in both models, as determined by reduced Ki-67 reactivity and significant lengthening of keratinocyte cell cycle transit times, while effectively promoting reepithelialization. The primary effect of GN was apparently to promote cell migration, as neither epidermal thickness nor epidermal differentiation was altered as a result of GN exposure in vivo or in vitro. Significantly enhanced epidermal reepithelialization was associated with alterations in expression of several keratinocyte integrin subunits. GN induced a significant increase in alpha5 expression. alpha5beta1 switching is a characteristic of the motile phenotype in the setting of cutaneous injury. Concomitantly, GN treatment also induced a dramatic (70%) decrease in the expression of the alpha3 subunit; alpha3beta1 binds laminin 5 and is associated with hemidesmosome formation and reestablishment of a nonmotile phenotype. Taken together, the GN-induced changes in integrin expression favor acellular migration. While the molecular mechanism of GN action on resident cells of the skin remains to be defined, these data suggest that GN administration which represses MMP activity in the wound and increases matrix synthesis also accelerates NHK motility and, thereby, may be a useful therapeutic agent for wound repair.

Animals↗

Gallium arsenide augments antigen processing by peritoneal macrophages for CD4+ helper T cell stimulation.

Gallium arsenide (GaAs) suppresses numerous immunologic functions of leukocytes at distal locations from the exposure site. The effect of direct GaAs exposure on peritoneal cells was examined by i.p. administration of the chemical. No alteration in the frequency of various cell lineages, including macrophages, B cells, CD4+ and CD8+ T cells, and granulocytes, occurred within the peritoneal population from GaAs-exposed mice. The ability of macrophages to function as antigen-presenting cells (APC) by processing a panel of soluble protein antigens was investigated by the stimulation of antigen-specific helper T cell hybridomas to secrete interleukin-2. On a per cell basis, GaAs-exposed macrophages were more efficient than vehicle control cells in activating the T cells with all native antigens examined. GaAs exposure increased the expression of major histocompatibility complex class II molecules, which are recognized by these T cells, on the surface of macrophages. However, the level of T cell activation with peptide fragments of the antigens, which do not require processing, was not enhanced with GaAs-exposed cells as APC. In contrast, the capability of latex bead-exposed macrophages to function as APC was comparable to that of vehicle control cells, suggesting that GaAs modulatory effects were not merely due to phagocytosis of particles. These findings suggest that direct GaAs exposure augments antigen processing, but not presentation, by macrophages perhaps by activating the cells, which may contribute to the immunotoxicity and inflammatory reaction caused by respiratory exposure to GaAs.

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↗

Direct exposure to gallium arsenide upregulates costimulatory activity of murine macrophages.

Gallium arsenide (GaAs) is an intermetallic semiconductor compound used in the electronics industry. Acute exposure of animals to GaAs systemically suppresses several immune functions while paradoxically causing inflammation at the exposure site. We investigated the effect of GaAs on costimulatory activity of murine peritoneal macrophages, 5 days after ip exposure. Costimulation by macrophages was determined by activation of CD4(+) helper T cell hybridomas to secrete interleukin-2 in the presence of immobilized monoclonal anti-CD3 antibody. Both peritoneal exudate cells (PEC) and resident peritoneal cells exposed to GaAs provided greater costimulation to the T cells than vehicle control cells. Resident peritoneal cells exposed to GaAs were also more efficient than latex bead-exposed cells, indicating that phagocytosis alone did not cause the GaAs effect. Double immunofluorescence staining and flow cytometric analysis revealed that GaAs-exposed PEC had increased cell surface expression of costimulatory B7-1 and B7-2 molecules and intracellular adhesion molecule-1 (ICAM-1) compared to controls. In addition to these molecules, resident peritoneal macrophages exposed to GaAs also expressed significantly higher levels of heat-stable antigen (HSA). Monoclonal antibodies specific for these costimulatory molecules significantly inhibited T cell activation, demonstrating that the molecules on GaAs-exposed cells were functional. In contrast, GaAs did not upregulate costimulatory molecules on splenic macrophages. These findings suggest that direct GaAs exposure improves macrophage costimulatory activity, possibly by activating the cells, which may contribute to respiratory inflammation caused by inhalation of GaAs particles.

Animals↗

Simultaneous gallium-67 citrate and technetium-99m sestamibi SPET in a case of myocardial lymphoma: comparison with echocardiography before and after chemotherapy.

A patient with diffuse large cell lymphoma involving the interventricular septum and the inferior ventricular wall was imaged with a simultaneous dual-isotope single-photon emission tomography (SPET) acquisition technique, using the radiotracers technetium-99m hexakis 2-methoxyisobutylisonitrile (sestamibi) and gallium-67 citrate, in conjunction with echocardiography, prior to and following the first course of chemotherapy. Simultaneous acquisition--with the advantage of displaying corresponding sets of SPET slices without any need for position correction--, supplemented by echocardiography, increased the accuracy of evaluation of the extent of disease and response to treatment.

Antineoplastic Combined Chemotherapy Protocols↗

Gallium-67 uptake in cutaneous sarcoidosis.

A case of abnormally increased gallium-67 uptake by cutaneous lesions in sarcoidosis is reported. The patient also had active sarcoidosis in lungs, periaortic lymph glands, salivary, and lachrymal glands.

Adult↗

Focal lung uptake of gallium-67 in patients with acquired immunodeficiency syndrome secondary to pneumocystis carinii pneumonia.

It is generally accepted that the lung uptake of 67Ga in patients with pneumocystis carinii pneumonia (PCP) is diffuse and bilateral. Three cases of focal lung uptake of 67Ga in AIDS patients with PCP but without other opportunistic infection are described. While focal lung uptake is characteristic of opportunistic infections other than PCP, we wish to emphasize that focal uptake of gallium in the chest does not rule out PCP and may represent its earliest stage of presentation.

Acquired Immunodeficiency Syndrome↗

Semi-quantitative gallium-67 lung scanning as a measure of the intensity of alveolitis in pulmonary sarcoidosis.

Gallium-67 (67Ga) lung scanning has been applied for some years in pulmonary sarcoidosis to assess the activity of the alveolitis. Interpreting the scans, however, is difficult due to the low uptake of 67Ga in the disease process relative to background activity. In this study we have measured the mean parenchymal lung activity of 67Ga and have compared the lung activity to that at three remote sites, the liver, the abdomen and the thigh. The results obtained were compared with the percentage of lymphocytes in broncho-alveolar lavage fluid. There was a very good correlation with the lung-to-thigh uptake measurements and a much poorer correlation with the lung-to-liver and the lung-to-abdomen measurements. It was observed that steroid therapy reduced dramatically the correlation between the broncho-alveolar lavage findings and the 67Ga scan measurements. The results suggest that in patients not on steroid therapy, the 67Ga lung-to-thigh measurements may be used, similarly to the broncho-alveolar lavage lymphocyte counts, to identify those with high-intensity alveolitis from those with low-intensity alveolitis.

Adult↗

Gallium scintigraphy in patients with adult T-cell leukemia lymphoma.

Gallium scintigraphy was evaluated in 25 patients with adult T-cell leukemia lymphoma (ATLL). Anterior and posterior images were obtained at 72 h after administration of 3 mCi 67Ga-citrate using a gamma camera (Maxi-Camera 400 T, General Electric Co.) with a medium energy standard parallel hole collimator. Abnormally high accumulations were observed in 17 out of 25 cases (superficial lymph node, 8; hilar and mediastinal lymph node, 7; paraaortic lymph node, 2; lung, 9; liver, 1; bone, 1). There were 10 malignant lesions detected by 67Ga scintigraphy in 9 out of 17 cases (superficial lymph node, 1; hilar and mediastinal lymph node, 6; paraaortic lymph node, 1; liver, 1; bone, 1). White blood cell count and serum LDH levels were raised in patients with abnormally high accumulations of 67Ga. In conclusion, 67Ga scintigraphy seemed to be a useful examination to detect malignant lesions in patients with ATLL.

Female↗

Transferrin receptors and gallium-67 uptake in vitro.

The relationship was studied between the number of transferrin-receptor positive cells and in vitro uptake of 67Ga and 125I-labeled transferrin in human cell lines, including two normal cell lines (WI-38 and foreskin fibroblasts), two transformed cell lines (AV-3 amnionic cells and Chang liver cells), and two neoplastic cell lines (HEp-2, larynx cancer and HeLa, cervical cancer). Transferrin receptors were determined by an indirect immunofluorescence technique based on their ability to bind purified human transferrin. Gallium-67 uptake was determined after a 24-h incubation of cells with Ga-67 in the presence and absence of transferrin (0-2.5 mg/ml). 125I-labeled transferrin uptake was also obtained after a 24-h incubation. The fraction of cells with transferrin receptors was low in normal cell lines (3% and 9%), intermediate with transformed cell lines (33% and 61%). Transferrin stimulated 67Ga uptake by all six cell lines. However, there was poor correlation between the number of transferrin-receptor positive cells and 67Ga uptake either in the presence (r = 0.21) or absence (r = 0.46) of human transferrin. Likewise, there was poor correlation between the number of transferrin-receptor positive cells and 125I-labeled transferrin uptake (r = 0.35). In contrast, the correlation between 67Ga uptake (in the presence of transferrin) and 125I-labeled transferrin uptake was highly significant (r = 0.96). These results suggest that human cell lines in culture are capable of both transferrin-dependent and transferrin-independent uptake of 67Ga.

Amnion↗

Gallium uptake in cerebrotendinous xanthomatosis.

In a patient with cerebrotendinous xanthomatosis, a rare familial sterol storage disease, increased uptake of gallium-67 was observed in the tendon xanthomas. This is considered to have resulted from the tumour-like proliferation of histiocytic cells in the xanthomas. Abnormalities in the white matter of the cerebellum and the brain stem observed by X-ray computed tomography and magnetic resonance imaging were not detected by 67Ga scintigraphy, possibly due to the small size of the CNS lesions.

Brain↗

Comparison of technetium-99m methoxyisobutylisonitrile and gallium-67 citrate scanning in the assessment of lymphomas.

The aim of this study was to compare the value of scintigraphy using technetium-99m methoxyisobutylisonitrile (MIBI) with that of scintigraphy using gallium-67 citrate in the assessment of Hodgkin's disease and non-Hodgkin's lymphoma and to relate these results with those of CT scan and MRI. Fifty-eight patients were included either for a follow-up examination or for monitoring of their treatment. Twenty-three residual masses were studied. A whole-body scan was performed, followed by single-photon emission computed tomography (SPET) 20 min after injection of 740 MBq of 99mTc-MIBI and 72 h after injection of 185 MBq of 67Ga citrate. The overall sensitivity of 99mTc-MIBI and 67Ga citrate was 71% and 68%, respectively, and the overall specificity was 76% and 44%, respectively. For residual masses, the sensitivity was 44% with both tracers and the specificity was 80% with 99mTc-MIBI and 53% with 67Ga citrate. The positive predictive values were 85% and 68% and the negative predictive values were 59% and 44%, respectively. The signal-to-background ratio was 1.5 for 99mTc-MIBI and 2 for 67Ga citrate. At present, 99mTc-MIBI cannot replace 67Ga citrate in the assessment of lymphomas.

Adult↗

Identification of AIDS-related tuberculosis with concordant gallium-67 and three-hour delayed thallium-201 scintigraphy.

Concordant gallium-67 and thallium-201 uptake has been described in malignant lesions. More recently, 201Tl accumulation has been described in some benign conditions. The authors report three HIV-positive patients who underwent 67Ga and 201Tl scintigraphy. These studies revealed concordant 67Ga and 201Tl uptake and tumour was erroneously diagnosed. All three patients were finally diagnosed as having tuberculosis.

AIDS-Related Opportunistic Infections↗

Computer quantitation of gallium 67 lung uptake in crocidolite (blue asbestos) workers of Western Australia.

Pulmonary inflammation has been evaluated in 43 crocidolite-exposed asbestos (ASB) workers and 12 control subjects, using a quantitative index of gallium uptake (GI). The GI was compared with chest roentgenographs (CXRs) graded by the ILO classification. The ASB workers included 15 with asbestosis (CXR greater than or equal to 1/0), 19 with a normal CXR (CXR 0/0), and 9 with equivocal CXR changes (CXR 0/1). In individuals with asbestosis the GI was 3.6 +/- 0.3 (mean +/- SEM), P less than 0.01 compared with exposed patients without asbestosis. In exposed patients with equivocal CXR changes (0/1) the GI was 3.1 +/- 0.3, and in exposed patients with a normal CXR (0/0) the GI was 2.4 +/- 0.2. The GI for subjects without lung disease was 1.2 +/- 0.2, P less than 0.01 compared with exposed patients without asbestosis. The scans were scored independently by two observers, and the correlation coefficient of the two sets of GI was 0.95. These data demonstrate that subjects with crocidolite-induced asbestosis and exposed patients with equivocal CXR changes or a normal CXR have significantly increased GI.

Asbestos↗

Pulmonary gallium-67 uptake in diffuse pulmonary calcinosis.

Diffuse pulmonary uptake of both technetium-99m- labeled methylene diphosphonate (99(m)Tc-MDP) and gallium (67Ga) citrate was noted in a patient with chronic renal failure and indicated the presence of pulmonary calcinosis. The uptake of 67Ga could be misinterpreted to represent abnormal uptake due to an opportunistic infection.

Adolescent↗

The role of gallium-67 scintigraphy in diagnosing sources of fever in ventilated patients.

OBJECTIVE: To evaluate the diagnostic value of gallium-67 scintigraphy in febrile ventilated patients by correlating the findings of 67Ga scintigraphy to sources of fever and pulmonary density, as determined by a comprehensive protocolized diagnostic evaluation. DESIGN: Prospective observational study. PATIENTS: Thirty-two intubated patients on mechanical ventilation for > or = 3 days with fever (> or = 38.3 degrees C) and a new or progressive density on chest radiograph. Twenty patients (21 tests) had adult respiratory distress syndrome (ARDS). INTERVENTION: Diagnostic evaluation for fever included bronchoscopy with protected specimen brushing and (protected) bronchoalveolar lavage (BAL); computed tomography (CT) of sinuses; cultures of blood, urine, and central lines; and CT of the abdomen in high-risk patients. MEASUREMENTS AND RESULTS: Uptake of 67Ga was reported as either focal or diffuse pulmonary uptake and extrapulmonary uptake. The combined causes of fever were pneumonia (9), fibroproliferation of late ARDS (7), abdominal process (4), sinusitis (4), urinary tract infection (3), and others (6). Causes of the pulmonary densities were pneumonia (9), ARDS (13), atelectasis (7), congestive heart failure (3), and empyema (1). Marked and diffuse pulmonary uptake was found only in patients with ARDS; however, it was not useful in discriminating those patients with pulmonary fibroproliferation as the sole cause of fever (p = 0.167) from those with infection. 67Ga scintigraphy was inadequate for detecting pneumonia but valuable in identifying extrapulmonary sites of infection in patients with ARDS (p = 0.021). CONCLUSIONS: 67Ga scintigraphy should be considered only as an adjunct diagnostic test in the febrile, ventilated patient who has no obvious source of fever, despite a negative evaluation that includes testing for pneumonia, sinusitis, and urinary tract infection, conditions that are rarely detected by 67Ga scintigraphy.

Adult↗