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Comparison of thallium-201 and gallium-67 scintigraphy in soft tissue and bone marrow multiple myeloma: a case report.

A 68-year-old female was referred for assessment of multiple myeloma. A large myelomatous infiltrate involving the left triceps muscle showed avid uptake on both thallium-201 and gallium-67 scintigraphy. Following radiotherapy, imaging with both radiopharmaceuticals showed resolution of disease; however, tumour recurrence in the bone marrow was seen only on thallium-201 imaging. This observation suggests that while soft-tissue myeloma shows similar appearances on thallium-201 and gallium-67 scintigraphy, both at baseline and following therapy, gallium-67 may not demonstrate bone marrow infiltration which is visualized on thallium-201 imaging. Therefore, thallium-201 appears to be superior to gallium-67 in evaluation of patients with multiple myeloma when soft tissues and bone marrow are involved.

Aged↗

Therapeutic potential of intravenous 67-gallium in non-Hodgkin's lymphoma.

67-gallium accumulates rather selectively in malignant lymphoid tissue. The isotope has a substantial cytotoxic effect in human-derived cell-lines. 67-gallium was given intravenously to 3 patients with end-stage, resistant large-cell lymphoma. Evaluation of tumour response was done by physical measurements, and CT-scanning together with gallium scintigraphy. Three weekly doses of 20, 40 and 60 mCi respectively caused persistent pancytopenia in 1 patient. Pancytopenia was not observed in 2 other patients given two 40 mCi doses 4 weeks apart. In all 3 patients, some response was noted, be it shortlived and different from site to site. 67-gallium has some cytostatic effect in large cell lymphoma. It seems feasible to start a phase I study to find a tolerable dose to be given every 4 weeks.

Adult↗

Galvanic corrosion and cytotoxic effects of amalgam and gallium alloys coupled to titanium.

The aim of this study was to examine and compare the galvanic corrosion of a conventional, a dispersed high-copper, and a palladium-enriched spherical high-copper amalgam and a gallium alloy coupled to titanium in saline and cell culture solutions, and to evaluate the effects of the couples on cultured cells. The potentials and charge transfers between amalgams and titanium were measured by electrochemical corrosion methods. Cytotoxicity of the couples, as indicated by the uptake of neutral red vital stain, was determined in 24-h direct contact human gingival fibroblast cell cultures. Results of this study indicated that before connecting the high-copper amalgams to titanium, the amalgams exhibited more positive potentials which resulted in initial negative charge transfers, i.e. corrosion of titanium. However, this initial corrosion appeared to cause titanium to passivate, and a shift in galvanic currents to positive charge transfers, i.e. corrosion of the amalgam samples. Lower galvanic currents were measured for the amalgam-titanium couples as compared to the gallium alloy-titanium couple. Coupling the conventional or the palladium-enriched high-copper amalgams to titanium did not significantly affect the uptake of neutral red as compared to cells not exposed to any test alloy. However, significant cytotoxic effects were observed when the dispersed-type high-copper amalgam and the gallium alloy were coupled to titanium. Even though the corrosion currents measured for these couples were less than gold alloys coupled to amalgam, these results suggest there is the potential for released galvanic corrosion products to become cytotoxic. These data warrant further investigations into the effects of coupling amalgam and gallium alloys to titanium in the oral environment.

Alloys↗

Assessment of activity of ocular sarcoidosis by gallium scanning.

Gallium (67Ga) citrate uptake over the orbits, parotid glands, and lungs was examined in six newly detected patients with sarcoidosis and 17 with chronic sarcoidosis. Six of 23 (26%) had uveitis, 18/23 (78%) decreased lacrimal secretion, and 13/16 (81%) epithelioid cell granulomas in conjunctival biopsies. Ten patients with other diseases served as controls. Only five patients had ocular complaints and two had enlarged parotid glands. 67Ga uptake over the orbits and parotids was measured by a quantitative computer based method. Gallium uptake was significantly higher over the orbits (p less than 0.001) and parotids (p less than 0.01) in the newly detected patients and in the parotids (p less than 0.01) in the chronic group than the corresponding uptake in the controls. We suggest that in sarcoidosis an increased 67Ga uptake in the orbital and parotid areas may be a phenomenon comparable to an increased 67Ga uptake in the lungs in active alveolitis. Gallium scan is a good method for revealing even symptomless ophthalmic sarcoid changes. However, in chronic sarcoidosis an equal or only slightly increased gallium uptake over the orbits compared with background activity does not exclude ocular sarcoid disease.

Adult↗

Oxidation of gallium sulfides by Thiobacillus ferrooxidans.

The bacterial oxidation of naturally occurring gallium-bearing chalcopyrite concentrate and a pure synthetic gallium (III) sulfide has been investigated at pH 1.8 and 35 degree C, using an active culture of Thiobacillus ferrooxidans. This oxidation process may proceed by direct or by indirect bacterial action. The highest dissolved gallium and copper concentrations were about 2.2 and 40.2 g/l, respectively. The order of the specific rate of oxygen uptake by T. ferrooxidans in approximately CuFES2 greater than or equal to gallium-bearing CuFeS2 greater than FeS2 greater than Cu2S greater than Cu2S greater than Ga2S3.

Copper↗

Correlation between gallium lung scans and fiberoptic bronchoscopy in patients with suspected Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome.

We retrospectively examined the sensitivity and specificity of gallium lung scans for detecting Pneumocystis carinii pneumonia in 22 patients with known or suspected acquired immune deficiency syndrome. Correlations were made between bronchoscopic results and gallium scan findings interpreted using a simple system (normal or abnormal) and a graded score (1 to 4). All 12 patients with Pneumocystis had abnormal scans by both interpretations (sensitivity, 100%). Five of these 12 patients had normal arterial PO2 values, chest roentgenograms, or both. In the 10 patients without Pneumocystis, scans were read as abnormal in 8 using the simple system (specificity, 20%) but were abnormal in only 1 using the grading system (specificity, 90%). Five patients with Pneumocystis pneumonia had scans and bronchoscopy after treatment; neither method of interpretation correlated with the presence of organisms. We conclude: (1) gallium scanning is a sensitive initial diagnostic test in patients with suspected Pneumocystis pneumonia; (2) a graded scoring system improves specificity; (3) an abnormal gallium scan (3 or greater) in patients with suspected Pneumocystis pneumonia is an indication for biopsy, even when the PO2 and/or chest roentgenogram are normal.

Acquired Immunodeficiency Syndrome↗

Regulation of transferrin receptor expression on human leukemic cells during proliferation and induction of differentiation. Effects of gallium and dimethylsulfoxide.

The association of transferrin receptor expression with cellular proliferation has been studied extensively, but a number of events have not been defined. We therefore assayed receptor on promyelocytic leukemia (HL-60) cells at early times after exposure to a stimulus for proliferation (subculture), as well as agents that either induce differentiation (dimethylsulfoxide [DMSO] ) or inhibit iron uptake (transferrin-gallium). Within 4 h after subculture, we found that a significant increase in total cellular immunoreactive receptor occurred that preceded by 8 h the increase in cell-surface transferrin binding. Automated fluorocytometric analysis of cells in an immunofluorescent assay indicated that increased surface receptor density appeared on cells in the S, G2, and M phases of the cell cycle. DMSO-treated cells proliferated at the same rate as untreated (control) cells for the first 72 h, but as early as 12 h after treatment transferrin receptor was significantly decreased (65% of control cells). Further decreases occurred at later time points until transferrin receptor was undetectable after 7 d, when proliferation had ceased, cells were arrested in G1 phase of the cell cycle, and myeloid differentiation occurred. After exposure to transferrin-gallium, proliferation ceased, but cells exhibited increased surface receptor and were arrested at S phase of the cell cycle without associated myeloid differentiation. We conclude that events preceding cell division provide the regulatory stimulus for the synthesis and subsequent appearance of the transferrin receptor on the cell surface. Additionally, decreased receptor expression may be important in causing cessation of proliferation and/or differentiation. Finally, the way in which gallium salts are currently being investigated as chemotherapeutic agents should be reevaluated in light of our findings concerning transferrin-gallium effects on cellular proliferation.

Antibodies, Monoclonal↗

Gallium nitrate inhibits calcium resorption from bone and is effective treatment for cancer-related hypercalcemia.

Approximately two-thirds of patients who receive the anticancer drug gallium nitrate develop mild hypocalcemia. To evaluate the mechanism of drug-induced hypocalcemia, we tested the effects of gallium nitrate upon in vitro release of 45Ca++ from explanted fetal rat bones. The drug significantly inhibited 45Ca++ release in response to stimulation with both parathyroid hormone and a lymphokine preparation with osteoclast activating factor activity. The inhibitory effects on bone resorption were both time- and dose-dependent. Later, in a pilot study, we treated 10 patients who had cancer-related hypercalcemia with gallium nitrate administered by continuous infusion. All patients responded by a reduction of total serum calcium to normal or subnormal concentrations (13.8 +/- 1.05 mg/dl, mean +/- SD pretreatment, to 8.03 +/- 1.03 mg/dl, mean posttreatment nadir). Our results indicate that gallium nitrate effectively treats cancer-related hypercalcemia and that it probably acts by inhibiting calcium release from bone.

Animals↗

Effects of gallium and mercury ions on transport systems.

Mercury was previously shown to exert toxic effects by influencing ion channels and transporters in the kidney and brain. Gallium alloys were suggested as less toxic restorative materials. To compare the toxicity of gallium ions with those of mercury ions, we applied gallium nitrate Ga(NO3)3 (0.1-100 microM and mercuric chloride (HgCl2) (0.001-10 microM) to Xenopus oocytes expressing mammalian ion channels and transport proteins. Mercury (10 microM) inhibited the K+-channels ROMK and HERG, the phosphate transporter NaPi-3, the amino acid transporter rBAT, the cation transporter OCT-2, and the osmolyte transporter BGT. It activated the I(Ks)-channel but did not affect the Na+-channel ENaC, the anion channel NaPi-1, and the glucose transporter SGLT-1. Gallium was without significant effect on the channels and on SGLT1, NaPi-3, and rBAT, but inhibited BGT and OCT-2. In conclusion, both Hg2+ and Ga3+ may exert toxic effects on transport systems, which may partially explain their cytotoxic effects.

Amino Acid Transport Systems↗

Cytotoxicity of gallium and indium ions compared with mercuric ion.

The use of mercury in dental amalgam restorations has become the subject of political controversy despite its long history of safe clinical use, and alternative materials based on gallium and indium rather than mercury have been developed. The biological safety of these metals must be evaluated, as part of their assessment as mercury substitutes. The cytotoxicities of mercury (II) nitrate, gallium (III) nitrate, and indium (III) nitrate were assessed at concentrations between 0.001 mmol/L and 1.0 mmol/L, using L929 mouse fibroblasts and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay and scanning electron microscopy. The mitochondrial dehydrogenase activity at each metal ion concentration as a percentage of the control was calculated from the absorbance values. The 50% inhibition concentration of mercury (II) nitrate was 0.35 mmol/L for cells in the rapid-growth phase and at confluence; gallium (III) nitrate and indium (III) nitrate did not significantly inhibit dehydrogenase activity in either the growing or confluent phase. Gallium and indium ions were not significantly toxic under the conditions of this assay.

Animals↗

Gallium nitrate inhibits accelerated bone turnover in patients with bone metastases.

Bone metastases are a major source of morbidity in patients with cancer. Previously, we found that gallium nitrate was a highly effective treatment for cancer-related hypercalcemia. Laboratory studies have shown that this drug inhibits bone resorption in vitro and that short-term treatment in vivo increases the calcium content of bone. We evaluated the clinical effects of gallium nitrate on biochemical parameters of increased bone turnover in 22 patients with bone metastases. Treatment with gallium nitrate for five to seven days caused a median reduction in 24-hour urinary calcium excretion of 66% relative to baseline measurements (P less than .01). Hydroxyproline (OHP) excretion was also significantly reduced (P less than .01). The greatest reduction in hydroxyprolinuria occurred in patients with high baseline excretion. Ionized serum calcium and serum phosphorous declined significantly after treatment (P less than .01 for each). Serum immunoreactive parathyroid hormone (PTH) increased significantly (P less than .01), as did serum levels of 1,25 (OH)2-vitamin D3 (P less than .05). Urinary phosphorous excretion and serum levels of 25-OH-vitamin D3 were not significantly changed. No major toxic reactions occurred as a result of this treatment. These results indicate that gallium nitrate significantly reduces biochemical parameters associated with accelerated bone turnover and that this agent may be useful for preventing pathologic conditions associated with bone metastases.

Adult↗

High frequency of benign mediastinal uptake of gallium-67 after completion of chemotherapy in children with high-grade non-Hodgkin's lymphoma.

We observed increased gallium-67 uptake in the mediastinum after completion of chemotherapy in 10 of 62 patients with non-Hodgkin's lymphoma. All 10 were under 15 years of age, yielding a frequency of 43% in this age group. The interval between cessation of chemotherapy and the development of increased gallium-67 uptake ranged from 1 to 8 months, and the abnormality persisted for 2 to 59 months. Serial chest x-rays were performed in all patients, and four of the 10 had transient widening of the mediastinum that remained within normal limits for the children's ages. Three patients had chest computed tomographic (CT) scans at the time of increased gallium-67 uptake, and one of the three had serial scans that showed a mediastinal mass consistent with thymic enlargement. All of the patients were asymptomatic and none were biopsied. All 10 remained well, with a mean follow-up of 52.5 months. The phenomenon we describe is probably due to "rebound" thymic hyperplasia, which is a benign and transient condition. We conclude that abnormal mediastinal gallium-67 uptake after completion of chemotherapy is likely to be benign and transient if the patients are young, have small non-cleaved-cell histology, are without other evidence of lymphoma recurrence, and do not have initial mediastinal involvement. Progressive widening of the mediastinum on chest x-ray is cause for suspicion and requires further evaluation. Serum lactate dehydrogenase (LDH) levels may not be helpful in differentiating a benign from a malignant process.

Age Factors↗

Comparison of thallium-201 and gallium-67 citrate scintigraphy in the diagnosis of pulmonary disease.

Gallium is presently used in the diagnosis of inflammatory, granulomatous, and neoplastic lung disease despite its many logistical problems. In contrast, thallium-201 scintigraphy, which was initially developed for myocardial imaging, offers the principal advantage of immediate imaging and diagnosis although it had not been investigated previously for use in pulmonary disease. In this study, thallium and gallium were prospectively compared with each other for the diagnosis of a variety of lung diseases. The overall concordance rate was 75%. Thallium was found to be significantly more sensitive than gallium for the entire group studied (N = 51, p < 0.006). In a subset of patients in whom a firm diagnosis was established, thallium was also found to be more sensitive, 86% vs 64%. The greater sensitivity of thallium-201 and its several inherent advantages suggest that thallium-201 should replace gallium-67 citrate as the radioisotope of choice for nuclear imaging of the chest.

Adolescent↗

Gallium-67 scintigraphy, bronchoalveolar lavage, and pathologic changes in patients with pulmonary sarcoidosis.

The intensity of gallium-67 scintiscans, lymphocyte counts in bronchoalveolar lavage fluid, and pathologic changes were studied in 26 patients with untreated pulmonary sarcoidosis. Noncaseating granulomas were recognized with significantly greater frequency in stage 2 (80 percent; 8/10 cases) than in stage 1 (43 percent; 6/14 cases). Alveolitis showed little relation to the roentgenographic stage. There was a strong correlation between the intensity of gallium uptake in pulmonary parenchyma and the detection rate of granuloma; however, the detection rate of alveolitis was not statistically different from the intensity of gallium uptake. A highly significant correlation was revealed between the lymphocyte counts in bronchoalveolar lavage fluid and the intensity of alveolitis. These observations suggest that the gallium uptake reflects mainly the presence of granuloma, and the lymphocyte count in bronchoalveolar lavage fluid reflects the intensity of alveolitis in patients with pulmonary sarcoidosis.

Adolescent↗

[Dimensional changes of silver and gallium-based alloy].

Gallium-based dental alloys were created with the aim of solving the problem of toxicity of mercury. The material shows mechanical properties similar to those of dental amalgam, but researches point out two unfavorable characteristics: great corrosion and excessive post-setting expansion, and the latter is capable of cracking dental structures. The aim of this study was to evaluate, during 7 days, the in vitro dimensional alteration of a gallium dental alloy (Galloy, SDI, Australia), in comparison with a dental amalgam containing zinc (F400, SDI, Australia), as a function of the contact with saline solution (0.9% NaCl) during the setting period. The storage experimental conditions were: storage in dry environment, immersion in saline solution and contamination during condensation. Additionally, the effects of contamination during the trituration of dental amalgam and the effects of protecting the surface of the gallium alloy with a fluid resin were studied. Specimens were stored at 37 degrees C +/- 1 degree C, and measuring was carried out, sequentially, every 24 h during 7 days. When the gallium alloy was either contaminated or immersed, an expansion significantly greater than that observed in the other experimental conditions was noticed after 7 days. The application of a fluid resin to protect the surface of the cylinders was able to avoid the increase in expansion caused by superficial moisture. The amalgam alloy did not show significant dimensional alterations, except when it was contaminated during trituration.

Alloys↗

Gallium scanning in cerebral and cranial infections.

Eighteen patients with cranial or intracranial infections were studied with technetium and gallium brain scans. Seven of 18 lesions were noted with gallium and not with pertechnetate, while the reverse pattern was not seen. Brain abscesses were visualized with gallium but not with pertechnetate in two of five cases. Osteomyelitis of the skull and mastoiditis showed intense gallium uptake in all cases, meningitis or cerebritis gave inconsistent results.

Bone Diseases↗

Gallium scanning in Paget's disease of bone: effect of calcitonin.

Calcitonin has been used in the treatment of Paget's disease of bone, and serum alkaline phosphatase level and 24 hr urinary hydroxyproline excretion have been used to follow therapeutic response. The radionuclide bone scan has been used as a visual indicator; however, there is some uncertainty as to its value in following changes in disease activity. Four patients with both serial technetium phosphate bone scans and serial gallium studies were studied. In each case the beneficial effect of calcitonin was demonstrated more accurately with gallium than with technetium diphosphonate. Since biochemical changes in Paget's disease are believed to be mediated at the cellular level and gallium uptake depends on cellular activity, it is proposed that gallium uptake is a more appropriate measure of the activity of Paget's disease than a noncellular marker such as a technetium-containing bone scan agent.

Calcitonin↗

Fatigue and tensile strength of dental gallium alloys after artificial saliva immersion.

Fatigue strength using the stair-case method and tensile strength of dental gallium alloys after artificial saliva immersion were measured for evaluating the effects of corrosive environment storage on the mechanical properties of the gallium alloys. The fatigue and the tensile strengths of both gallium alloys stored in artificial saliva were significantly decreased after 12-month storage, while those stored in air increased with storage period. The fracture surfaces of the specimens in artificial saliva showed not only metallic luster but also dark areas. In the dark area, the matrix might have dissolved during immersion. These results suggested that the concern over corrosion resistance of gallium alloys still remained.

Corrosion↗