Gallium Accumulation Research Articles

Comparison of magnetic resonance imaging and 67gallium scintigraphy in the evaluation of posttherapeutic residual mediastinal mass in the patients with Hodgkin's lymphoma

Introduction Detection of residual disease following the completion of primary treatment in Hodgkin's lymphoma (HL) patients diagnosed with mediastinal tumor mass has an exceptional importance in the assessment of therapeutic response. Magnetic resonance imaging (MRI) and 67gallium ( 67Ga) scintigraphy can be used to identify active tumor tissue in the mediastinal residuum. Aims To evaluate: the accuracy of MRI and 67Ga scintigraphy in the prediction of clinical HL relapse/progression; congruence of findings and the probability of mediastinal disease relapse/progression regarding to the detection of active/inactive tissue by both imaging methods. Materials and methods Thirty HL patients with abnormal mediastinal tissue following the completion of primary treatment were examined by MRI and 67Ga scintigraphy. Positive findings were: high signal intensity on unenhanced T2-weighted images on MRI and the abnormal accumulation of gallium on scintigraphy or SPECT. These findings were compared with the clinical follow-up. Results Sensitivity, specificity, accuracy, positive and negative predictive values were: 75.0%, 96.2%, 93.3%, 75.0%, 96.2% in MRI and 50.0%, 88.5%, 83.3%, 40.0%, 92.0% in 67Ga scintigraphy. Discrepant results concerning the mediastinal tissue activity were found in 3 of 30 patients (10%). No statistically significant differences were found between both imaging methods in sensitivity, specificity and accuracy. Estimated 2-years progression free survival (PFS) for patients without and with active residual mediastinal tissue by MRI was 96% and 25% ( p = 0.0001), respectively. The probability of 2-years PFS in the cases with negative and positive findings on 67Ga scintigraphy was 92% and 60% ( p = 0.026), respectively. Conclusion Although MRI showed better results than 67Ga scintigraphy in the assessment of residual mediastinal tissue activity in HL patients after primary treatment, the difference between these methods was not statistically significant. Both methods could be included in the standard restaging protocol.

Usefulness of late gadolinium enhancement combined with MRI and 67-Ga scintigraphy in the diagnosis of cardiac sarcoidosis and disease activity evaluation

We report a case in which late gadolinium enhancement (LGE) and 67-Ga scintigraphy were useful for the diagnosis of cardiac sarcoidosis and for the evaluation of the disease activity. The patient was a 60-year-old woman who had been diagnosed as having eye sarcoidosis when she was 48. Two years previously her electrocardiogram had shown abnormalities but the coronary angiography had shown normal coronary arteries; however, an aneurysm was detected in the apical portion by left ventriculography. A II degree AV block was noted on the electrocardiogram and she was referred to us for further detailed evaluation. Since the biopsy findings of skin eruptions on both eyelids indicated an epithelial cell granuloma, she was diagnosed as having cutaneous sarcoidosis. On the 67-Ga scintigram, myocardial accumulation of gallium was recognized, and on cardiovascular magnetic resonance (CMR), LGE was recognized. She was diagnosed as cardiac sarcoidosis and steroid therapy started with 30 mg prednisolone. The myocardial accumulation of gallium on the 67-Ga scintigram disappeared after the 30th day of steroid therapy. On the other hand, no changes in LGE patterns were seen after steroid therapy. In this case, LGE was useful for the diagnosis of cardiac sarcoidosis, and 67-Ga scintigram was useful for the evaluation of the disease activity. This case shows that both imaging techniques are important for the diagnosis of cardiac sarcoidosis and evaluation of the disease.

Asymmetric Lower Extremity Muscle Activity on a Gallium Scan

A 17-year-old girl with a history of Hodgkin disease showed increased gallium accumulation in the region of the right hip and reduced uptake in the muscles of the right lower extremity. Increased gallium accumulation in the right hip was attributed to avascular necrosis and the reduced gallium activity was attributed to disuse atrophy of the right lower extremity secondary to avascular necrosis (confirmed on the CT scan).

A case of primary gastric Burkitt-like lymphoma in the early stage diagnosed by endoscopic mucosal resection

Dear Editor: Burkitt-like lymphoma (BLL) is a rare and rapidly progressive type of lymphoma that usually occurs in young males. In the Revised European– American Lymphoma (REAL) classification, BLLs are described as diffuse B-cell lymphomas with a high proliferative rate and molecular biological characteristics considered to be borderline between those of classic Burkitt lymphoma (BL) and those of diffuse large B-cell lymphoma (DLBCL). Although the gastrointestinal tract is one of the most common regions for extranodal malignant lymphomas, primary gastrointestinal lymphomas are rare. BL and BLL occur in various gastrointestinal sites, and 30–80% of patients have involvement of the small bowel or colon and rectum, especially the ileocecal region. Involvement of the stomach occurs in only 10% of the patients, and almost all of the cases were detected in the late stage as a bulky mass located in the abdomen or other gastrointestinal sites. Here we report a case of primary gastric BLL in the early stage. To the best of our knowledge, this is the first report of a case of BLL presenting with a submucosal tumor (SMT) that was diagnosed by endoscopic mucosal resection (EMR). In June 2003, a 52-year-old Japanese man underwent upper gastrointestinal endoscopy and a SMT measuring 20 mm was detected in the gastric antrum. Endoscopic pictures with indigocarmine spraying dye clearly revealed the surface of the SMT. It was extensible, nodular, and glossy with telangiectasia, and no ulcer was seen on the surface. The tumor was elastic and immovable, and four biopsy specimens showed inflammatory cell (neutrophil and plasma cell) invasion with infection by Helicobacter pylori. Endoscopic ultrasonography (EUS) (20 MHz) was performed to examine the inner parts of the SMT. The tumor was found to be a homogeneous hypoechoic lesion and to be located in the submucosal layer. A computed tomography (CT) scan showed neither bulky mass nor lymph node metastasis. On scintigraphy, there was no accumulation of gallium except in the stomach. No abnormality was detected in other portions of the alimentary tract by small-bowel examination and colonoscopy. Since the proper muscular layer of the tumor was thought to be intact, we thought that this tumor was resectable, and EMR was performed for diagnosis. Pathologically, the cut end of the resected specimen was negative. The tumor cells showed a very high mitotic rate and a nuclear variability in the submucosal layer. A starry-sky appearance and mediumsized lymphoid cells showing a jigsaw puzzle effect of cytoplasmic borders were seen in the tumor tissues. Immunohistochemically, tumor cells were positive for L-26 and K. Nosho (*) . M. Shitani . F. Takahashi . Y. Ikeda . A. Goto . H. Yamamoto . Y. Arimura . T. Ishida . T. Endo . K. Imai First Department of Internal Medicine, Sapporo Medical University, S.-1, W.-16, Chuo-ku, Sapporo, 060-8543, Japan e-mail: nosho@sapmed.ac.jp Tel.: +81-11-6112111 Fax: +81-11-6112282

CIGSSe thin film PV modules: from fundamental investigations to advanced performance and stability

A process for high efficiency large area Cu(In,Ga)(Se,S) 2 (CIGSSe) thin film solar modules is developed applying rapid thermal processing and controlled sodium doping. Continuous optimization aims at sufficient process maturity for a successful transfer into cost-effective mass production. The pilot line yields aperture area efficiencies of 11% (average) for 30×30 cm 2 modules and a certified champion efficiency of 13.1% for the first 60×90 cm 2 demonstrator module (unencapsulated). First Cd-free 30×30 cm 2 circuits yield up to 11.9% efficiency applying CBD-Zn(S,OH)-buffer layers. Investigations on the absorber formation by structural, compositional and electrical characterization will be given. Models for the Ga and S distribution will be discussed and experimentally verified. A favorable double band gap grading structure is accomplished by controlled sulfur profiling and by a process induced gallium accumulation towards the back electrode. The stability of the frameless low-cost packaged pilot line modules against humidity is confirmed externally by passing the damp heat test sequence according to IEC 61646.

CIGSSe thin film PV modules: from fundamental investigations to advanced performance and stability

A process for high efficiency large area Cu(In,Ga)(Se,S) 2 (CIGSSe) thin film solar modules is developed applying rapid thermal processing and controlled sodium doping. Continuous optimization aims at sufficient process maturity for a successful transfer into cost-effective mass production. The pilot line yields aperture area efficiencies of 11% (average) for 30×30 cm 2 modules and a certified champion efficiency of 13.1% for the first 60×90 cm 2 demonstrator module (unencapsulated). First Cd-free 30×30 cm 2 circuits yield up to 11.9% efficiency applying CBD-Zn(S,OH)-buffer layers. Investigations on the absorber formation by structural, compositional and electrical characterization will be given. Models for the Ga and S distribution will be discussed and experimentally verified. A favorable double band gap grading structure is accomplished by controlled sulfur profiling and by a process induced gallium accumulation towards the back electrode. The stability of the frameless low-cost packaged pilot line modules against humidity is confirmed externally by passing the damp heat test sequence according to IEC 61646.

Selenium effects on gallium arsenide induced biochemical and immunotoxicological changes in rats

The influence of selenium (6.3 and 12.6 μmol/kg, intraperitoneally) on the disposition of gallium and arsenic and a few gallium arsenide (GaAs) sensitive biochemical variables was studied in male rats. Concomitant administration of Se and GaAs (70 μmol/kg, orally, 5 days a week for 4 weeks) significantly prevented the accumulation of arsenic while, the gallium concentration reduced moderately in the soft organs. The biochemical (haematopoietic and liver) and immunological variables however, responded less favorably to selenium administration. Most of the protection was however observed with the dose of 12.6 μmol rather than at 6.3 μmol. The results thus suggest a few beneficial effects of selenium in preventing the appearance of signs of GaAs toxicity like preventing inhibition of blood δ-aminolevulinic acid dehydratase (ALAD), hepatic malondialdehyde (MDA) formation and the accumulation of gallium and arsenic concentration.

#699 Intense gallium accumulation in the stomach after initiation of treatment for Hodgkinʼs lymphoma associated with helicobacter pylorri infection

#699 Intense gallium accumulation in the stomach after initiation of treatment for Hodgkinʼs lymphoma associated with helicobacter pylorri infection

Assessment of pulmonary microvascular permeability by Gallium-67 in neutropenic patients with adult respiratory distress syndrome

The adult respiratory distress syndrome (ARDS) which involves increased protein permeability oedema of the lungs is thought to result, in general, from microvascular injury by activated neutrophils. However, it can also occur during neutropenia. The 1-hour pulmonary accumulation of Gallium (Ga)-67, corrected for blood volume, the so-called pulmonary leak index (PLI), is elevated during ARDS in non-neutropenic patients. Whether this is a measure of protein permeability, and truly neutrophil independent, is open to question since intravenous injected Ga-67 may not firmly bind to circulating transferrin but to lactoferrin present in, or derived from, neutrophils. Three patients with circulating white blood cell counts between 0.1 and 0.7 × 109 /l in the course of treatment for haematological malignancy were studied: Patients 1 and 2 at the time of ARDS, and Patient 2 also during recovery from ARDS and neutropenia. Patient 3 had normal lung function and a normal chest X-ray, and was studied before and on the ...

Phosphorus doping in molecular beam epitaxial grown silicon and silicon/germanium using a GaP decomposition source

Donor-doping in silicon molecular beam epitaxy (MBE) is still an open problem, due to the low solid solubility and the strong segregation behavior (Sb,As) or to the high vapor pressure of the doping elements (P,As). Based on its high solubility, elemental P 2 would be the best candidate for heavy n-type doping. A new source has been applied to incorporate electrically active phosphorus during growth higher than 10 20 cm −3 in Si and SiGe. The incorporation probabilities into Si and strained SiGe will be compared. The dependence of segregation/diffusion processes of phosphorus on growth temperature during the MBE will be shown. No surface accumulation of phosphorus or gallium were observed. SIMS investigations on undoped Si layers reveal no P or Ga “memory effect” of the UHV equipment.

Gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy.

To determine the predictive value of gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality treatment. A retrospective study was performed of 48 patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality therapy. Patients were monitored with whole-body planar scans (34 patients) or chest single-photon-emission computed tomography (SPECT) plus planar abdominal imaging studies (14 patients). Scans were performed at diagnosis, following three to eight cycles of chemotherapy, and after the end of treatment. The value of gallium scans in modifying treatment and predicting outcome was assessed. All patients studied at the time of diagnosis had abnormal gallium accumulation in the mediastinum. After chemotherapy, four patients had residual mediastinal activity; two patients with persistent activity on planar scans failed to enter remission and died of disease; two other patients with abnormal activity only seen on SPECT had therapy modified and remain in remission. After chemotherapy, 44 patients had a normal gallium scan. Twelve patients with negative scans relapsed, including nine patients with recurrence above the diaphragm. The use of gallium scans after several courses of chemotherapy resulted in a modification of treatment in four patients, including two patients who are apparently cured. However, after negative scans, 20% of patients relapsed above the diaphragm. These results suggest that gallium imaging, including SPECT, is of limited value in predicting disease sterilization, although the number of patients studied with SPECT was small. At present, the major value of gallium scans is to identify patients who may benefit from a modification of treatment.

Distribution of trace levels of therapeutic gallium in bone as mapped by synchrotron x-ray microscopy.

Gallium nitrate, a drug that inhibits calcium release from bone, has been proven a safe and effective treatment for the accelerated bone resorption associated with cancer. Though bone is a target organ for gallium, the kinetics, sites, and effects of gallium accumulation in bone are not known. We have used synchrotron x-ray microscopy to map the distribution of trace levels of gallium in bone. After short-term in vivo administration of gallium nitrate to rats, trace (nanogram) amounts of gallium preferentially localized to the metabolically active regions in the metaphysis as well as the endosteal and periosteal surfaces of diaphyseal bone, regions where new bone formation and modeling were occurring. The amounts measured were well below the levels known to be cytotoxic. Iron and zinc, trace elements normally found in bone, were decreased in amount after in vivo administration of gallium. These studies represent a first step toward understanding the mechanism(s) of action of gallium in bone by suggesting the possible cellular, structural, and elemental "targets" of gallium.

Gallium-67 scanning in patients with malignant pleural mesothelioma.

The findings of Gallium-67 scans in eleven patients with malignant pleural mesothelioma were reviewed and compared to those of chest CT findings. All patients had an abnormal thoracic Ga-67 accumulation. Six out of 11 showed a diffuse accumulation over the entire involved hemithorax and a localized uptake was shown in 5. A marked diffuse thickening of pleura in the absence of adequate gallium accumulation was observed in one patient. Two out of 11 had a reduction of gallium uptake after having combination chemotherapy. These results suggest that a diffusely increased uptake over the entire involved hemithorax is the most characteristic finding of Ga-67 scan in malignant pleural mesothelioma, and that Ga-67 scans may be helpful as a valuable indicator of the proper therapy. However, the superiority of Ga-67 scan to thoracic CT as a means of determining the extent of disease process could not be verified.

Studies on the67Ga uptake mechanism by Ehrlich ascites tumor cells

In order to obtain more information concerning the mechanism of Gallium (67Ga) accumulation in malignant tissue, an investigation was carried out using Ehrlich ascites tumor cells. Chlorpromazine, a phospholipid stabilizer decreased the uptake of 67Ga and Calcium 45 (45Ca) by the cells at low dose, but increased them at high dose. On the other hand, the uptake of both radionuclides by the cells was inhibited by ruthenium red, a Ca ATPase inhibitor in a dose dependent manner. The time course of 67Ga and 45Ca uptake were quite different from each other. Moreover, the subcellular distribution patterns of 67Ga and 45Ca were also different from each other; 67Ga accumulated in the lysosomal fraction and 45Ca mainly in the mitochondrial fraction. These results suggest that there may be a commonality for 67Ga and 45Ca uptake by the tumor cells, whereas the behaviour of these two radionuclides in the cells is dissimilar.

On the mechanism of gallium accumulation in tumours. Isolation of N-hydroxypeptides

With the use of A SEP-PAK Alumina N cartridge, peptide fractions containing the hydroxamate moiety have been isolated from tumour-tissue homogenate. It is therefore postulated that N-hydroxypeptides might play a role in the accumulation of gallium-67 in tumours. The biodistribution of several 67Ga-labelled hydroxamate peptide fractions is determined. Although their biodistribution differs from that of 67Ga-citrate no enhancement in tumour accumulation is observed indicating that they do not act like tumour-specific siderophores.

Gallium Accumulation in the Stomach

Accumulation of tracer by the stomach is a frequent incidental occurrence on gallium scans. Gastric concentration of Ga-67 equal to or greater than that seen in the liver was observed in approximately 10% of patients in a large series. Although a few of these patients had known or subsequently demonstrated gastric pathologic conditions, most had no clinically or radiographically identifiable gastric disease.

Intractable heart failure, conduction disturbances and myocardial infarction by massive myocardial invasion of malignant lymphoma

A patient with malignant lymphoma who developed congestive heart failure, conduction disturbances and myocardial infarction is presented. Two-dimensional echocardiography revealed marked thickening of the left ventricular wall, where the gallium scan correspondingly showed an abnormal accumulation. Irradiation to the mediastinum resulted in a dramatic decrease in ventricular wall thickness and disappearance of the gallium accumulation. Postmortem examination confirmed previous lymphomatous involvement of the myocardium. Combined techniques, including echocardiography and gallium scan, can be valuable for noninvasive detection and follow-up of myocardial involvement in patients with malignant lymphoma.

Determination of Gallium Concentration in “Blood-Free” Tissues Using a Radiolabeled Blood Marker

Radioiodinated serum albumin has been used as a blood marker to define and quantitate physiological volumes for 12 organs and tissue types. The concentration of gallium-67 in “blood-free” tissues of rats was also determined at various times after intravenous administration. Tissues were divided into two kinetically distinguishable types based on reported nonuniform distribution of the blood marker and the gallium distribution observed in the present study. Gallium distribution into the liver and spleen was observed to be slow, with a discernable accumulation phase followed by monoexponential elimination. In contrast, gallium accumulation into the stomach, small and large intestines, heart, lung, skin/adipose tissue, and muscle was rapid and elimination was monophasic.

Renal gallium accumulation in mice with acute immune complex glomerulonephritis

67Ga uptake and heparan sulfate (HS) content were investigated during the recovery of mouse kidney from acute immune complex glomerulonephritis induced by daily injections of bovine serum, and the binding of 67Ga to glomerular basement membrane (GBM) was studied in vitro. The results were as follows. 67Ga uptake in the kidney increased after the start of bovine serum injection, and peaked on the 20th day. The uronic acid content in 1.2 M NaCl-soluble fraction (which contained predominantly HS) and the hydroxyproline content (an index of collagen) were increased at the 10th day, reaching a maximum at the 20th day. This pattern of HS content was essentially the same as that of 67Ga accumulation in the kidney. Urinary protein and γ-GTP activity peaked at the 5th day, and these patterns were different from that of 67Ga uptake. 67Ga binding to GBM was significantly inhibited by treatments with HS-degrading enzyme (heparitinase), nitrous acid, trypsin or papain. However, the binding to GBM was unaffected by treatment with chondroitinase ABC. These results provide further evidence that the 67Ga-binding substance in tumor tissues and inflammatory lesions is probably HS.

Lacrimal gland accumulation of 67Ga-citrate in patients with Sjögren's syndrome.

The extent of 67Ga accumulation in the two lacrimal glands in patients with keratoconjunctivitis sicca (KCS) of Sjögren's syndrome was studied. Of the two main groups one consisted of 69 subjects without ophthalmic complaints (control group), the other consisted of 26 patients with KCS of Sjögren's syndrome. Of the 26 patients with KCS, 7 had been diagnosed as probable KCS (probable sub-group) and the other 19 had been diagnosed definite KCS (definite sub-group). About 3 mCi (111 MBq) 67Ga-citrate was injected IV into each subject and this was followed by scintigraphy at 24, 48, and 72 h after the injection of 67Ga. A positive finding in the lacrimal gland was noted in 64 of 69 subjects (92.7%) in the control group and in 7 of 7 patients (100%) with probable KCS. Three of 19 patients with definite KCS (15.7%) showed positive findings under scintigraphy. When the scintigraphic finding in the lacrimal gland is not positive in patients with suspected KCS of Sjögren's syndrome, they can then be diagnosed with little risk as definite KCS cases. Shirmer's test was performed on subjects in the probable and definite groups. There was statistical significance between the positive and equivocal or negative scintigraphic finding and Schirmer's values. These results suggest a correlation between gallium accumulation in the lacrimal gland and the tear production.