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PubMed2005

Gallium-inducible transferrin-independent iron acquisition is a property of many cell types: possible role of alterations in the plasma membrane.

BACKGROUND: We have previously shown that human myeloid cell types can acquire large amounts of iron (Fe)3+ from low-molecular-weight chelates by a process that is independent of adenosine triphosphate and dramatically increased by gallium (Ga) and other multivalent cationic metals. METHODS: To provide further insight into the mechanism responsible and its relevance to other cellular systems, we investigated Fe acquisition from nitrilotriacetic acid (NTA) by several myeloid and nonmyeloid cell lines in the presence and absence of Ga. RESULTS: Most nonmyeloid cells examined exhibited similar ability to acquire Fe from NTA. Ga increased the apparent maximum velocity (Vmax), with minimal changes in apparent Michaelis constant (Km), of all cell lines. Both erythrocytes and erythrocyte ghosts acquired Fe from NTA, which increased with Ga exposure, analogous to nucleated cells. However, liposomes made from phospholipids did not exhibit Ga-inducible Fe association. Enzymes that modify surface proteins and carbohydrates did not alter HL-60 cell Fe acquisition. Modifying HL-60 membrane fatty acid content had only a minimal effect. Ga exposure did not change membrane potential or fluidity. However, electron microscopy suggested that Ga alters plasma membrane physical properties. CONCLUSION: Multivalent cations appear to induce changes in cell membranes that may alter their interaction with Fe3+ and probably other multivalent cations.

Animals↗
PubMed1992

Cytotoxicity of corroded gallium and dental amalgam alloys. An in vitro study.

The cytotoxicity of one gallium and three different dental amalgam alloys was assessed in a cell culture system. Two evaluation methods were used, the filter method and an extraction method. Before being tested, set specimens of the alloys were stored in 0.9% NaCl solution for 1 and 10 weeks, to corrode. The alloys showed various degrees of cytotoxicity, ranging from mild to marked. Differences were found between the two testing methods, but in most cases no major differences in cytotoxicity were found between the Ga alloy and the amalgams. The results encourage further study and development of the Ga alloy, which is mercury-free.

Biocompatible Materials↗
PubMed1981

Alteration of gallium distribution in the rat using periodically related elements: enhanced early imaging.

Complexes of carrier-gallium and indium were administered to normal rats and rats with tumors 2 to 6 hours after an injection of carrier-free 67Ga citrate in order to determine their effect on the distribution of 67Ga. Both Ga and In rapidly and significantly decreased the blood activity. Imaging with the same dosage schedule showed decreased activity in soft tissue and viscera, and increased activity in bone, kidney, and bladder. In animals with tumor high doses of carrier-Ga were shown to deplete tumor activity as well as activity in viscera and soft tissues. Moderate doses of carrier-Ga allowed blood and soft tissue clearing with no significant loss of tumor activity. When In citrate was administered to animals with tumors 2 hours after administration of 67Ga, tumor activity continued to increase while soft tissue and visceral activity decreased. Simultaneous injection of In citrate and 67Ga drastically altered the distribution of 67Ga. Two hours after the injection activity was present only in the tumor, kidney, bladder, and bone. This rapid clearance of non-productive Ga brings forth the potential for use of short lived, positron emitting 68Ga coupled with emission tomography.

Animals↗
PubMed1996

Monitoring bulky mediastinal disease with gallium-67, CT-scan and magnetic resonance imaging in Hodgkin's disease and high-grade non-Hodgkin's lymphoma.

Treatment of both Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL) with bulky presentation at diagnosis frequently results in residual masses detected radiologically. Conventional diagnostic radiology and computed tomography (CT) are generally unable to detect the differences between tumor tissue and fibrosis. Gallium-67-citrate (67Ga) SPECT and magnetic resonance imaging (MRI) can potentially differentiate residual active tumor tissue and fibrosis. Thirty-three patients with HD or HG-NHL presenting with bulky mediastinal disease were studied with CT, 67Ga SPECT, and MRI (only for 16 patients) at diagnosis, after two-thirds of their chemotherapy, at the end of chemotherapy, and after radiotherapy in order to evaluate the mediastinal region on the basis of persistence of residual masses and activity of pathological tissue. After treatment, all patients with 67Ga-negative (30/33) disease are still in continuous complete response. Among the three 67Ga-positive patients, 2 relapsed within one year and another one is still alive without evidence of disease. Regarding MRI, two patients were found to be positive, one of them concomitant with 67Ga-positivity; both patients survive in complete response. In lymphoma patients with bulky mediastinal presentation, the 67Ga SPECT remains the preferable imaging technique for monitoring and differentiating the eventual active residual tumor. In combination, CT and 67Ga SPECT represent a suitable complete imaging approach to the radiological diagnosis which may be useful in these particular patients. MRI could probably be considered as a second-line method and from our data would be used only in selected cases because of the high cost, accessibility, and lower specificity as opposed to 67Ga SPECT in evaluating potentially active residual disease.

Adolescent↗
PubMed1999

The usefulness of high dose (7-10mci) gallium (67Ga) scanning to diagnose Richter's transformation.

Gallium (67Ga) scan was performed in 29 CLL patients with chronic lymphocytic leukemia who were suspected on clinical grounds to have Richter's transformation (RT). Of 29 patients, nine had a positive 67Ga scan; seven of these had a subsequent biopsy that verified large-cell lymphoma or Hodgkin's disease. The other two patients underwent biopsies that revealed fungal infections, a known cause of 67Ga uptake. Two patients had biopsies that were consistent with RT but showed no affinity to 67Ga. One false negative resulted five days after chemotherapy, a known cause of diminished 67Ga uptake. The other occurred within a small infraorbital mass, containing only 10% centroblasts, which is below the level of detection for 67Ga scanning. Subsequent 67Ga scans in both patients revealed 67Ga avid lesions, which demonstrated RT upon biopsy. This technique was more strongly predictive of RT than was measurement of serum B-2 microglobulin or serum lactate dehydrogenase levels. 67Ga scanning is very useful in localizing an optimal site for biopsy to document RT; it may also have the potential to help assess response to treatment, predict recurrence, and contribute to long-term follow-up in this subset of patients.

Aged↗
PubMed1997

Intracarotid infusion of RMP-7, a bradykinin analog, and transport of gallium-68 ethylenediamine tetraacetic acid into human gliomas.

The bradykinin analog, RMP-7, was investigated for its ability to increase selectively the transport of 68Ga ethylenediamine tetraacetic acid (EDTA) into recurrent malignant gliomas in nine patients. For each patient, two position emission tomography (PET) studies (one with and one without RMP-7) were performed. For studies with RMP-7, 10 to 300 ng/kg of the compound was infused into the supraophthalmic carotid artery over 15 minutes. In each PET study, a sequence of PET scans was initiated simultaneously with an intravenous bolus of 68Ga EDTA (5-10 mCi). Arterial samples were taken to provide the input function. All PET scans were coregistered to the magnetic resonance (MR) images of the patient. Regions of interest were defined for tumor and normal tissue regions on MR images and were copied to the coregistered PET dynamic images to provide brain tissue-time activity curves. The constant (Ki) for the transport of gallium-68 from plasma to brain tissue was determined using a simple compartmental model. Intracarotid infusion of RMP-7 significantly increased transport into tumor regions with an average increase of 46 +/- 42% (mean +/- standard deviation, p < 0.05). Permeability in normal tissue regions was not significantly increased. Tumors in three of six patients treated with 300 ng/kg RMP-7 and carboplatin had at least a 50% reduction in tumor volume as measured by MR imaging. Intracarotid infusion of RMP-7 is a novel technique for selective delivery of antitumor compounds into brain tumors.

Adult↗
PubMed2000

Positron emission tomography in lymphoma: comparison with computed tomography and Gallium-67 single photon emission computed tomography.

With the advent of positron emission tomography (PET), metabolic imaging has become a reality for tumor staging and monitoring response to therapy in lymphoma. Increased Fluorine-18 fluorodeoxyglucose ([(18)F]FDG) uptake in lymphomas has been well documented in the literature; it is based upon elevated glycolysis and longer residence time of FDG in malignant cells compared to most normal tissues. This suggests that in tumor staging, FDG-PET may be more sensitive and specific than the anatomic imaging modalities. Computed tomography (CT) is the standard imaging modality for the staging and restaging of lymphoma, and Gallium-67 ((67)Ga) scintigraphy has played an important role in monitoring response to therapy and follow-up of patients. Published results suggest that FDG-PET is superior to (67)Ga imaging and may be equal or superior to CT for the detection of nodal as well as extranodal involvement in lymphoma.

Aged↗
PubMed2005

Activity of gallium nitrate in refractory peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCLs) are post-thymic malignancies characterized by an aggressive clinical course and an inferior outcome with standard therapies. The authors report significant clinical activity of infusional gallium nitrate in a patient with stage IV PTCL disease refractory to chemotherapy.

Aged↗
PubMed1976

The value of gallium-67 scanning in upper abdominal lymphomas.

A series of 77 gallium-67 citrate (67Ga citrate) scans of the abdomen revealed lymphoma in 12 cases (nine of non-Hodgkin's lymphoma, three of Hodgkin's disease). Scanning was undertaken (i) to confirm the suspicion of lymphoma, or (ii) as part of a staging procedure when the diagnosis of lymphoma had been established, or (iii) as a follow-up investigation after treatment of lymphoma. The diagnosis of lymphoma in the upper part of the abdomen is difficult with conventional techniques such as lymphography, and it is in this area that 67Ga citrate scanning is shown to be of value.

Abdominal Neoplasms↗
PubMed1977

Error in anti-DNA antibody radioimmunoassay after gallium scanning.

Significant interference with the accurate measurement of anti-DNA antibodies occurs after gallium-67 scanning. The observed effect is dependent on the radioimmunoassay used. False-negative results are observed with a modified Farr assay whereas false-positive results are noted in the millipore filter assay. These spurious values are the result of persistent radioactivity in the patients' sera after administration of 67Ga citrate.

Antibodies, Antinuclear↗
PubMed1999

Hodgkin's disease: internal mammary lymph nodes relapse diagnosed by gallium-67 scintigraphy.

This article presents the case of a 62-year-old man with treated Hodgkin's disease who had internal mammary lymph nodes relapse after a complete initial response. These masses were gallium avid. These findings were explained by histologically documented Hodgkin's relapse, the first such case reported in that localization without chest wall involvement. The literature on mediastinal Hodgkin's disease and diagnostic procedures are reviewed.

Breast↗
PubMed1999

Treatment and clinical management of primary mediastinal large B-cell lymphoma with sclerosis: MACOP-B regimen and mediastinal radiotherapy monitored by (67)Gallium scan in 50 patients.

To evaluate the efficacy of a combined modality treatment (MACOP-B plus mediastinal radiotherapy) and the advantages of Gallium-67-citrate single-photon emission ((67)GaSPECT) over computed tomography (CT) for restaging in patients with primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis. Between 1989 and 1998, 50 previously untreated patients with PMLBCL with sclerosis (70% with bulky mass) were treated with MACOP-B regimen plus mediastinal radiotherapy. The radiologic clinical stage with evaluation of tumor size included CT and (67)GaSPECT at diagnosis, after chemotherapy, and after radiotherapy. Forty-three patients (86%) achieved a complete response and 7 were nonresponders to treatment. For the imaging evaluation, only 47 patients were evaluable because 3 had disease progression during chemotherapy. After treatment, 3/5 (60%) patients with positive (67)GaSPECT and negative CT scan relapsed, as against 0/21 (0%) with negative (67)GaSPECT and CT scan. Twenty-one patients had a positive CT scan: of these, the 4 with positive (67)GaSPECT all progressed, whereas there were no relapses among the 17 with negative (67)GaSPECT. After radiotherapy, there was a decrease of positive CT (from 33 to 21 cases) and of positive (67)GaSPECT (from 31 to 9 cases). Relapse-free survival rate was 93% at 96 months (median 39 months). In patients with PMLBCL with sclerosis, MACOP-B plus radiation therapy is a very useful first-line treatment and radiation therapy may play an important role. As regards restaging, (67)GaSPECT should be considered the imaging technique of choice at least in patients who show CT positivity.

Adult↗
PubMed2000

Comparative study of the toxic effects of gallium arsenide, indium arsenide and arsenic trioxide following intratracheal instillations to the lung of Syrian golden hamsters.

Toxic effects of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were studied in male Syrian golden hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) particles were instilled intratracheally twice a week a total of 16 times, while InAs (7.7 mg/kg) was instilled a total of 14 times. As a control, hamsters were treated with the vehicle, phosphate buffer solution. During the instillation period, the cumulative body weight gain of the InAs-, but not the GaAs- or As2O3-treated hamsters was suppressed significantly, when compared with the control group. Slight to severe inflammatory responses were observed in the lung for all treatment groups. The most severe inflammatory change, characterized by an accumulation of neutrophils and macrophages, exudation, thickness of the pleura and fibrotic proliferation was found in the InAs-treated hamsters. Extensive alveolar or bronchiolar cell hyperplasia with or without keratinizing squamous cell metaplasia was observed in almost all the InAs-treated hamsters. Furthermore, squamous cell metaplasia or squamous cell hyperplasia developed in some of the InAs-treated hamsters, but not in the GaAs- or As2O3-treated hamsters. Slight to mild lesions were found in the convoluted tubules of the kidney in both the GaAs and InAs groups. From the present study, the toxic potency of these particles was provisionally estimated to be in the following order: InAs > GaAs > As2O3, at the dosage level used in this study. Furthermore, there was evidence that InAs particles could induce pulmonary, renal or systemic toxicity, and as such, InAs particles may produce pulmonary precancerous change when instilled intratracheally into hamsters.

Animals↗
PubMed1975

Gallium-67-citrate scanning for the localization and staging of lymphomas.

One-hundred-eight 67Ga-citrate scans were evaluated in Hodgkin's and non-Hodgkin's lymphomas for staging, diagnosis of recurrence, and for determing the results of treatment. Accuracy as confirmed by comparing the scans with pathologic material or roentgenologic and clinical findings was found to be 83%. Known lymph node involvement was diagnosed correctly in 87% but accuracy was only 48% for extranodal areas. Bone lesions were diagnosed correctly in 83% compared with only 48% of lesions of the lungs and liver. Scans were 75% accurate in 28 patients scanned for initial staging. False negatives were present in 12%; recurrent tumor in an area of prior radiation therapy appeared to be the most common cause. There were 5% false positives. Gallium scanning is a useful adjunct to other methods of detecting lymphoma.

Adolescent↗
PubMed2001

Immunoscintigraphy with positron emission tomography: gallium-68 chelate imaging of breast cancer pretargeted with bispecific anti-MUC1/anti-Ga chelate antibodies.

Pretargeting techniques that are based on the sequential administrations of bispecific antitumor/antimetal chelate antibodies (BS-MAbs), a blocker to saturate the anti-chelate binding sites of the BS-MAb still present in the circulation, and the radiolabeled chelate are suitable to increase tumor-to-normal tissue contrasts and enable positron emission tomography (PET) as an imaging method. As demonstrated in the nude mouse model, a combination of pretargeted immunoscintigraphy and PET markedly improved the detection of tumor xenografts. With the presented preliminary clinical trial, we attempted to assess the efficacy of pretargeting and PET for breast cancer localization in patients. The BS-MAb used for pretargeting was synthesized from the F(ab')(2) fragments of the anti-MUC1 MAb 12H12, which reacts with the vast majority of breast tumors, and the F(ab') fragments of an anti-gallium (Ga) chelate MAb via a mixed functional chemical linker. For labeling of the Ga-chelate, we used the short-lived positron emitter Ga-68 (t(1/2), 68 min; beta(+), 88%). The dose and time schedule of pretargeting was deduced from previous animal experiments. Ten patients with biopsy-proven, primary breast carcinoma were infused with 10 mg of the BS-MAB: Eighteen h later, they received i.v. injections of 10.7 mg of a blocker and, 15 min later, 9.6 microg of the Ga chelate labeled with 230-300 MBq of (68)GA: PET imaging was started 60-90 min after injection of the (68)Ga chelate. Average tumor-to-blood and tumor:normal breast tissue ratios were 0.9 and 3.0 at 1 h postinjection. Tumor uptake amounted to approximately 0.003% iD/g corresponding to a standard uptake value of approximately 2. Blood clearance of the (68)Ga chelate showed a t(1/2) beta of approximately 100 min. Fourteen of 17 known lesions, averaging 25 +/- 16 mm in size, were clearly visualized as foci of increased activity with PET. No false-positive but three false-negative readings were obtained. An enhanced, bilateral activity uptake in the whole breast parenchyma, found in 4 of the 10 patients, compromised the recognition of these tumor sites. Although the shedding of the MUC1 antigen and the comparatively low tumor affinity of the BS-MAb, common to all anti-mucin MAbs, proved not to be optimal for increasing tumor:tissue ratios with a pretargeting technique, PET imaging offered better sensitivity for the detection of breast cancer at low tumor contrasts than conventional immunoscintigraphy. This could be demonstrated by the clear visualization of tumor sites 10 mm in size, which contrasted only by a factor of 2 from surrounding normal breast tissue.

Adult↗
PubMedDate not supplied

[Evaluation of motor and sensory neuroconduction of the median nerve in patients with carpal tunnel syndrome treated with non-coherent light emitted by gallium arsenic diodes].

INTRODUCTION: The treatment selection in the carpal tunnel syndrome according to the damage of the median nerve is important and all of these have adverse effects. A good alternative without undesired reactions is irradiation of the carpal tunnel with not coherent light between 920 and 940 nm emitted by gallium arsenide diodes, resembling the physic and therapeutic laser effects. PATIENTS AND METHODS: Twenty-six female patients with idiopathic middle carpal tunnel syndrome were irradiated 15 minutes daily during three weeks. The median nerve motor and sensitive neuroconduction was studied before and immediately after the treatment. RESULTS: The abnormal neuroconduction variables (latency, amplitude and velocity conduction) did not modify when treatment concluded, in spite of all the patients reported disappearance of pain and numbness in damaged hands. CONCLUSIONS: Not coherent light does not change the fibers functional state explored by conventional neuroconductions techniques. It remains to know if this light produces fine fibers improvement.

Arsenicals↗
PubMed1975

Scintigraphic demonstration of abscesses with radioactive gallium labeled leukocytes.

Autologous peripheral blood leukocytes, labeled in vitro with 67Ga citrate, have been studied in 20 patients as a radioactive carrier for the scintigraphic visualization of septic inflammatory areas. 67Ga citrate was added to venous whole blood; following incubation, the blood was centrifugated, and the packed cells were reinfused. Scintiscans were obtained four and 24 hours later. The inflammatory process was demonstrated in nine of nine patients with confirmed sepsis. Eleven patients without sepsis had normal scans. There were no false-negative scans and one-false-positive scan. The selective accumulation of the gallium labeled leukocytes in areas of septic inflammation was sufficient to allow scintigraphic demonstration of the inflammatory area.

Abscess↗
PubMedDate not supplied

Comparison of 18F-fluoro-2-deoxyglucose positron emission tomography and gallium-67 citrate scintigraphy for detecting malignant lymphoma.

This study evaluates and compares the accuracy of positron emission tomography with 18F-fluoro-2-deoxyglucose (FDG-PET) and gallium-67 citrate (Ga-67) scintigraphy in identifying disease sites in patients with malignant lymphoma at initial diagnosis or relapse. Histology subgroups included low (n=5), intermediate (n=6), high-grade (n=5) non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) (n=14). Ann-Arbor staging included 7 patients in stage I, 8 in stage II, 9 in stage II, 6 in stage IV and 11 extra-nodal. In this study, before any therapy, 25 contemporaneous FDG-PET and Ga-67 scintigraphies were performed on patients with either NHL (16) or HD (14). One hundred and eleven sites of disease were correlated on a site-by-site basis in corresponding areas of FDG-PET and Ga-67 scintigraphy. Discordant FDG-PET and Ga-67 scintigraphic findings were correlated with CT/MRI and clinical evaluation. FDG-PET detected malignant lymphoma in 24/25 patients (sensitivity: 96.0%). There was a false-negative FDG-PET result in only 1 patient with low-grade gastric malignant lymphoma. Ga-67 scintigraphy detected malignant lymphoma in 18/25 patients (sensitivity: 72.0%). There were false-negative Ga-67 scintigraphic results in 4 cases with low-grade non-Hodgkin's lymphoma, 2 cases with bone or bone marrow involvement, and 3 smaller disease sites. FDG-PET upstaged 6 patients in whom Ga-67 scintigraphy detected disease sites partially. In imaging lymphoma prior to therapy, FDG-PET had a higher sensitivity and detected significantly more disease sites when compared with Ga-67 scintigraphy in the initial evaluation of this group of patients. Upstaging of patients with FDG-PET may result in a change in treatment strategy. However, evaluation of the final sensitivity, specificity and accuracy of these imaging modalities will need a further study with a larger patient number.

Adult↗