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PubMed1986

Gallium-67 activity in bronchoalveolar lavage fluid in sarcoidosis.

Roentgenograms and gallium-67 scans and gallium-67 counts of BAL fluid samples, together with differential cell counts, have proved to be useful in assessing activity and lung involvement in sarcoidosis. In active pulmonary sarcoidosis gallium-67 scans are usually positive. Quantitation of gallium-67 uptake in lung scans, however, may be difficult. Because gallium-67 uptake and cell counts in BAL fluid may be correlated, we set out to investigate gallium-67 activity in BAL fluid recovered from patient of different groups. Sixteen patients with recently diagnosed and untreated sarcoidosis, nine patients with healthy lungs, and five patients with CFA were studied. Gallium-67 uptake of the lung, gallium-67 activity in the lavage fluid, SACE and LACE levels, and alpha 1-AT activity were measured. Significantly more gallium-67 activity was found in BAL fluid from sarcoidosis patients than in that from CFA patients (alpha = .001) or patients with healthy lungs (alpha = .001). Gallium-67 activity in BAL fluid could be well correlated with the number of lymphocytes in BAL fluid, but poorly with the number of macrophages. Subjects with increased levels of SACE or serum alpha 1-AT showed higher lavage gallium-67 activity than did normals, but no correlation could be established. High gallium-67 activity in lavage fluid may be correlated with acute sarcoidosis or physiological deterioration; low activity denotes change for the better. The results show that gallium-67 counts in BAL fluid reflects the intensity of gallium-67 uptake and thus of activity of pulmonary sarcoidosis.

Bronchi↗

PubMed1998

The role of the gallium scan in primary extranodal lymphoma.

UNLABELLED: The purpose of this study was to examine the factors influencing gallium scan positivity for patients with primary extranodal lymphoma and to examine the role of the gallium scan in staging the disease and assessing response to initial treatment. METHODS: Ninety-two patients with extranodal lymphoma who had a gallium scan were reviewed. The influences of tumor site, size, grade and the presence of clinically detectable disease after biopsy on the rate of gallium scan positivity were analyzed. The role of the gallium scan in staging and selecting treatment was assessed. Nineteen patients had a gallium scan to assess their response to treatment, and its predictive value was reviewed. RESULTS: The overall gallium scan positivity (sensitivity) rate was 70%. This rate was low in patients whose extranodal lymphoma occurred in skin, intestine and testis, or was low grade (0%-25%). When these patients were excluded, the rate rose to 88%. Gallium scan positivity was not related to the presence of clinically detectable disease after biopsy and there was insufficient data about tumor size to determine a relationship. The gallium scan increased the disease stage in six patients (7%) and changed the initial treatment in six patients (7%). The gallium scan became negative in 15 (79%) of those patients who had a gallium scan to assess their response to treatment. All but two of these patients remain alive with a median follow-up of 3.75 yr. CONCLUSION: The gallium scan was rarely positive for patients with skin, intestinal, testicular and low-grade lymphomas, but was otherwise comparable to lymphoma arising in lymph nodes. The result affected staging or treatment in seven patients (8%). After treatment, an initially-positive gallium scan usually became negative, a conversion associated with a favorable outcome.

Citrates↗

PubMed2002

In vivo and in vitro modulation of carp (Cyprinus carpio L.) phagocyte oxidative burst activity by gallium.

Since gallium is a metal ion used in semiconductor industry, the toxicological effects were previously evaluated in mammals but the ecotoxicological impacts remain unknown. In term of ecotoxicological risk assessment, the median lethal concentration (LC50 for 96 h of gallium to carp (Cyprinus carpio L.) and the oxidative response of carp phagocytes after the fish were exposed to sublethal levels of gallium were determined. The LC50 of gallium on C. carpio at 96 h was estimated as 96.25 +/- 14.3 mg/L. To determine the effect in vivo of gallium on the phagocyte response, fish were exposed for 96 h to 5 or 50 mg Ga(3+)/L. Carp maintained for 48 or 96 h in water containing 50 mg/L gallium had a significant fall in phagocyte oxidative burst activity in comparison with controls, as well as decreased leukocyte number in blood and increased cytotoxicity. To determine the effect in vitro of gallium on the phagocyte response, isolated phagocytes were exposed for 5 or 15 min to 50 nM, 500 nM, or 5, 50, 100, or 200 microM of Ga(3+). The oxidative burst was increased after in vitro incubation of phagocytes with 50 or 500 nM gallium for 15 min or with 500 nM gallium for 5 min. Moreover, for 50, 100, or 200 microM gallium, the oxidative burst activity of carp phagocytes was significantly decreased. Results indicate that the lethal toxicity of gallium for carp of gallium is not as high as for other metal ions. However, gallium was immunosuppressive for carp at the highest concentrations used (from 50 microM) in vivo and in vitro. At low concentrations, it could be an immunostimulant as observed in vitro.

Animals↗

PubMed2006

Gallium-induced cell death in lymphoma: role of transferrin receptor cycling, involvement of Bax and the mitochondria, and effects of proteasome inhibition.

Gallium nitrate is a metallodrug with clinical efficacy in non-Hodgkin's lymphoma. Its mechanisms of antineoplastic action are not fully understood. In the present study, we investigated the roles of transferrin receptor (TfR) targeting and apoptotic pathways in gallium-induced cell death. Although DoHH2 lymphoma cells displayed a 3-fold lower number of TfRs than CCRF-CEM lymphoma cells, they were 3- to 4-fold more sensitive to gallium nitrate. Despite a lower TfR expression, DoHH2 cells had greater TfR cycling and iron and gallium uptake than CCRF-CEM cells. In other lymphoma cell lines, TfR levels per se did not correlate with gallium sensitivity. Cells incubated with gallium nitrate showed morphologic changes of apoptosis, which were decreased by the caspase inhibitor Z-VAD-FMK and by a Bax-inhibitory peptide. Cells exposed to gallium nitrate released cytochrome c from mitochondria and displayed a dose-dependent increase in caspase-3 activity. An increase in active Bax levels without accompanying changes in Bcl-2 or Bcl-X(L) was seen in cells incubated with gallium nitrate. The endogenous expression of antiapoptotic Bcl-2 was greater in DoHH2 cells than in CCRF-CEM cells, suggesting that endogenous Bcl-2 levels do not correlate with cell sensitivity to gallium nitrate. Gallium-induced apoptosis was enhanced by the proteasome inhibitor bortezomib. Our results suggest that TfR function rather than TfR number is important in gallium targeting to cells and that apoptosis is triggered by gallium through the mitochondrial pathway by activating proapoptotic Bax. Our studies also suggest that the antineoplastic activity of combination gallium nitrate and bortezomib warrants further investigation.

Antineoplastic Agents↗

PubMed1983

Quantitative gallium scanning in pulmonary sarcoidosis.

Pulmonary parenchymal involvement in sarcoidosis is due to noncaseating granuloma, fibrosis or both. To assess the granulomatous activity in pulmonary sarcoidosis, we performed gallium-67 citrate scans in 41 patients with sarcoidosis and in 13 non-sarcoid patients, who were free of pulmonary disease and served as controls. Gallium score, a measure of gallium accumulation in lung parenchyma, was obtained from the sum of activity indices (ratio of accumulated gallium activity over a chest quadrant and soft tissues of the mid-thigh) from each of the quadrants over the anterior and posterior aspects of the chest. The gallium score in patients with sarcoidosis was significantly higher than the gallium score in controls. The gallium scores in patients with sarcoidosis, with radiographically apparent pulmonary infiltrate were significantly higher than the scores in the patients with no radiographic evidence of pulmonary parenchymal involvement. The gallium scores in patients not receiving corticosteroids were significantly higher compared to patients who were receiving corticosteroids, and furthermore, the gallium scores fell significantly when corticosteroids were initiated. There was a significant correlation between serum angiotensin-converting enzyme (SACE) activity and gallium score. In 11 patients, 27 sequential gallium scans were performed and changes in gallium score correlated well with the changes in SACE activity and clinical assessment. These findings suggest that quantitative evaluation of gallium scans may be useful in assessing granulomatous activity of pulmonary sarcoidosis and following its response to therapy.

Adrenal Cortex Hormones↗

PubMed2002

Gallium uptake in complicated pancreatitis: a predictor of infection.

OBJECTIVE: A retrospective evaluation was performed of the use of gallium imaging in patients with known severe pancreatitis to detect infection in pancreatic and peripancreatic fluid collections. MATERIALS AND METHODS: Gallium-67 single-photon emission computed tomography (SPECT) studies were retrospectively reviewed in patients with complicated pancreatitis. Only patients who had undergone interventional procedures within 10 days of the scanning were included in our analysis. A total of 23 scans from 20 patients were reviewed. SPECT imaging was typically performed 48-72 hr after injection of the gallium. All studies were correlated with conventional CT findings. Findings from subsequent interventions (results of aspiration, Gram stains, or cultures) were used as evidence of infection. RESULTS: Twenty patients underwent either percutaneous or surgical drainage within 10 days of their gallium scanning. One patient underwent gallium scanning on three different occasions and underwent three different interventional procedures after each of the gallium scans, bringing the total number of cases in our study to 23. Of these 23 cases, 18 patients (78%) with gallium scans showing positive findings for infection had infected fluid; five patients (22%) with negative findings for infection on gallium scans had sterile fluid (p < 0.00001). No false-positive scans were found among our study cases, and we found no correlation between the uptake of gallium and the presence or absence of pancreatic necrosis. CONCLUSION: Gallium does not actively accumulate in all patients with severe pancreatitis, and gallium uptake does not correlate with the presence or absence of necrosis. In patients with severe pancreatitis complicated by fluid collections or inflammatory masses, gallium SPECT is a useful predictor of infection and can be used to help guide subsequent intervention. Gallium SPECT allows targeting sites of infected fluid in patients with multiple fluid collections and potentially obviates intervention in patients with sterile fluid collections.

Acute Disease↗

PubMed1992

Regulatory effects of gallium on transferrin-independent iron uptake by human leukemic HL60 cells.

Gallium, a pharmacologically important metal, resembles iron with respect to transferrin (Tf) binding and Tf receptor-mediated cellular uptake. In the present study, we examined the effect of gallium on Tf-independent iron uptake by HL60 cells. In contrast to the inhibitory effect of Tf-gallium on Tf-iron uptake, gallium nitrate, in a time-, temperature-, and concentration-dependent manner, stimulated Tf-independent uptake of iron-nitrilotriacetic acid (Fe-NTA). Preexposure of cells to gallium followed by removal of gallium also resulted in sustained stimulation of iron uptake. The anti-Tf receptor monoclonal antibody 42/6 blocked Tf-iron uptake, but had no effect on gallium-induced stimulation of Tf-independent iron uptake. Gallium increased the number of cell membrane iron-binding sites, without a change in their affinity for iron. Ferric chloride stimulated Tf-independent gallium uptake. Although gallium nitrate inhibited cell growth in Tf-free medium, cellular proliferation was restored by Fe-NTA. Gallium and iron appear to share the same Tf-independent cellular uptake system in HL60 cells. Exposure of cells to gallium results in the activation of cell membrane non-Tf iron carriers that may play a role in overcoming the Tf-independent growth-inhibitory effects of gallium.

Antibodies, Monoclonal↗

PubMedDate not supplied

Scintigraphic pattern of planar gallium scan in wound infection after colorectal surgery.

BACKGROUND: The incidence of postoperative wound infection is higher after colorectal surgery than after other surgical procedures. No studies have evaluated the usefulness of gallium 67 scintigraphy for detecting wound infection after colorectal surgery. We investigated the clinical potential of gallium imaging for detecting wound infection after colorectal surgery. METHODS: Fifty patients who had fever after colorectal surgery were enrolled in this study. All patients had open surgical incisions at the midline of the abdomen. Planar gallium scintigraphy was performed 24 h, and then as needed, after the injection of 111 MBq (3 mCi) Ga 67 citrate. All scans were interpreted by two physicians specializing in nuclear medicine. Intensities of gallium uptake at the surgical wound were recorded as grades 0 (no uptake), 1 (less than liver uptake), 2 (equal to liver uptake), or 3 (greater than liver uptake). When the intensity of gallium uptake was equal to or greater than grade 2, gallium uptake was classified as two patterns: regular and irregular. RESULTS: Eighteen patients were diagnosed with wound infection. When interpretation was based on only gallium-uptake intensity, the diagnostic sensitivity, specificity, and accuracy of the gallium scan were 100%, 75%, and 84%, respectively. When interpretation was based on gallium-uptake intensity and pattern, the diagnostic sensitivity and specificity were 94.4% and 96.9%, respectively. The diagnostic accuracy had increased, from 84% to 96%. CONCLUSION: Planar gallium scan is useful for detecting wound infection after colorectal surgery. Gallium-uptake pattern and intensity are important for interpreting planar gallium scans.

Adolescent↗

PubMed2000

A pharmacokinetic and phase II study of gallium nitrate in patients with non-small cell lung cancer.

This study investigated the pharmacokinetics and activity of gallium nitrate in non-small cell lung cancer when 700 mg/m2 was given as a 30-min infusion with prehydration every 2 weeks. Gallium was measured in plasma and urine using flameless atomic absorption spectrophotometry, and pharmacokinetics of total and ultrafilterable gallium were calculated. Twenty-five patients with non-small cell lung cancer received 1-12 (median 2) courses of gallium nitrate every 2 weeks. Of 21 patients evaluable for response, 1 partial response was recorded, 4 patients had stable disease. and 16 had progressed. The most serious toxicities were renal impairment and optic neuritis. Hypocalcaemia was recorded in 3 patients. The mean C(max) was 15.2 +/- 3.1 microg/ ml (range 9.5-21.2). Most gallium remained ultrafilterable for the first 10 h, after which plasma protein binding increased, and at 48 h only 11% was present as ultrafilterable gallium. The elimination profiles of both total and ultrafilterable gallium were biphasic, and the distribution phase consisted of ultrafilterable gallium, with a distribution half-life of 1.4 h. Total gallium plateaued at 1.9 microg/ml at between 8 and 12 h, and the estimated elimination half-life was 63 h. The elimination half-life of ultrafilterable gallium was 16.5 h. Inter- and intra-patient variability in pharmacokinetics was minimal. A mean of 50 +/- 14% of the gallium dose was excreted in the urine within 48 h. A short infusion of gallium nitrate achieving high peak plasma concentrations results in little efficacy in non-small cell lung cancer.

Adult↗

PubMed1993

Gallium nitrate inhibits alkaline phosphatase activity in a differentiating mesenchymal cell culture.

The effect of gallium nitrate on alkaline phosphatase activity in a differentiating chick limb-bud mesenchymal cell culture was monitored in order to gain insight into the observation that rachitic rats treated with gallium nitrate failed to show the expected increase in serum alkaline phosphatase activity. Cultures maintained in media containing 15 microM gallium nitrate showed drastically decreased alkaline phosphatase activities in the absence of significant alterations in total protein synthesis and DNA content. However, addition of 15 microM gallium nitrate to cultures 18 h before assay for alkaline phosphatase activity had little effect. At the light microscopic and electron microscopic level, gallium-treated cultures differed morphologically from gallium-free cultures: with gallium present, there were fewer hypertrophic chondrocytes and cartilage nodules were flatter and further apart. Because of altered morphology, staining with an antibody against chick cartilage alkaline phosphatase appeared less extensive; however, all nodules stained equivalently relative to gallium-free controls. Histochemical staining for alkaline phosphatase activity was negative in gallium-treated cultures, demonstrating that the alkaline phosphatase protein present was not active. The defective alkaline phosphatase activity in cultures maintained in the presence of gallium was also evidenced when cultures were supplemented with the alkaline phosphatase substrate, beta-glycerophosphate (beta GP). The data presented suggest that gallium inhibits alkaline phosphatase activity in this culture system and that gallium causes alterations in the differentiation of mesenchymal cells into hypertrophic chondrocytes.

Alkaline Phosphatase↗

PubMed2004

Gallium compounds as antineoplastic agents.

PURPOSE OF REVIEW: The purpose of this review is to provide an outline of the basic and clinical information on gallium nitrate as an antineoplastic agent. Although early clinical trials indicated that gallium nitrate had activity against lymphoma and bladder cancer, its subsequent development centered primarily on its effect on bone metabolism and not on its antineoplastic activity. As a result, the drug was approved for the treatment of hypercalcemia of malignancy. However, pharmaceutical production of gallium nitrate ceased during the late 1990s, bringing several gallium-based clinical trials to a halt. Gallium nitrate has recently become commercially available, thus reopening the door for clinical trials evaluating it as an antineoplastic agent. RECENT FINDINGS: Multicenter clinical trials have recently been conducted to reevaluate gallium nitrate for the treatment of lymphoma. An oral formulation of gallium is also in development. Gallium's mechanisms of action include its binding to transferrin, targeting to transferrin receptors on lymphoma cells, and inhibiting ribonucleotide reductase. Recent investigations show that gallium activates caspases and induces apoptosis through the mitochondrial pathway, whereas complementary DNA microarray studies suggest that changes in intracellular trafficking pathways may be important in gallium resistance. SUMMARY: Gallium nitrate has demonstrated activity against lymphoma and bladder cancer, which is likely the result of selective targeting of these malignancies. An important property of gallium nitrate is that it is not myelosuppressive and it lacks cross-resistance to other drugs. Further investigations are needed to understand better its molecular targets and to determine its clinical efficacy in combination with other drugs.

Antineoplastic Agents↗

PubMed1995

Gallium scans in the evaluation of residual masses after chemotherapy for seminoma.

PURPOSE: To assess the ability of gallium scans to determine whether residual masses consist of viable tumor or necrotic fibrous tissue after chemotherapy for seminoma. PATIENTS AND METHODS: Thirty-two patients were enrolled and 27 were assessable. Patients receiving first-line or salvage chemotherapy had gallium scans performed during their first and last scheduled course of chemotherapy and results were compared with restaging computed tomographic (CT) scans and subsequent clinical outcome. RESULTS: Of 27 assessable patients, 22 received first-line chemotherapy (group A) and five salvage chemotherapy (group B). Eight patients were not gallium-avid before chemotherapy despite obvious clinical and radiographic evidence of metastatic seminoma. Eighteen of 19 gallium-positive patients had a persistent mass postchemotherapy on abdominal CT. Of 16 patients in group A whose tumors were gallium-avid, all 16 had normalized gallium scans after chemotherapy. However, two of these 16 patients recurred in their original disease site. In group B, there were three patients with gallium-avid tumors and all three had normalized scans postchemotherapy. Two patients who were not gallium-avid (one each in group A and B) also developed recurrent disease. Twenty-four of 27 patients are alive with no evidence of active disease at a median follow-up time of 18 months, including 20 with more than 1 year of follow-up data. CONCLUSION: Eight of 27 patients had false-negative gallium scans at the time of diagnosis. All nineteen gallium scans that were initially positive reverted to normal after chemotherapy. Two of 19 patients' follow-up gallium scans were false-negative. We therefore feel that gallium scans have minimal value in the prechemotherapy or postchemotherapy evaluation of metastatic seminoma.

Adult↗

PubMed2004

The utility of gallium scintigraphy in the evaluation of fever of unknown origin.

BACKGROUND: Gallium scintigraphy is frequently used in the evaluation of fever of unknown origin, although its utility has been addressed in only a few studies. OBJECTIVES: To evaluate the utility of gallium scintigraphy in the evaluation of patients with FUO in our department. METHODS: We reviewed the charts of all patients from our department who had undergone gallium scintigraphy during the years 1995-2002 for the evaluation of FUO and who met the criteria for the definition of FUO. Demographic, clinical and laboratory data in addition to the results of gallium scintigraphy were documented. The patients were divided into two groups: those with a normal gallium study (group 1) and those with an abnormal gallium study (group 2). The second group was further divided into two groups: those whose gallium study results contributed to the diagnosis of the cause of FUO (group 2A) and those whose gallium study results did not (group 2B). RESULTS: A total of 102 patients met the study criteria. The male: female ratio was 54:48 and the mean age +/- SD was 62.4 +/- 20 years. A final diagnosis had been reached in 63 patients (62%), among whom the etiology was infectious in 54%, neoplastic in 19% and immunologic/ rheumatic in 16%. Forty-one patients (40% of all the patients) (group 2) had an abnormal gallium scintigraphy, and in only 21 patients (21% of all the patients) (group 2A) did the gallium study results contribute to the diagnosis of the cause of FUO. However, in only two patients from group 2A (2% of all the patients in our study) was the contribution of gallium study considered significant or crucial to the diagnosis of the cause of FUO. CONCLUSIONS: The utility of gallium scintigraphy in the evaluation of FUO is very limited.

Adolescent↗

PubMed2001

Uptake of gallium-67 citrate in clean surgical incisions after colorectal surgery.

Non-specific accumulation of gallium-67 citrate (gallium) in uncomplicated surgical incisions is not uncommon. It is important to know the normal pattern of gallium uptake at surgical incision sites in order to properly interpret the gallium scan when investigating possible wound infection in patients who have undergone abdominal surgery. We studied 42 patients without wound infection after colorectal surgery and performed gallium scans within 40 days after surgery. Patients were divided into three groups according to the interval between the operation and the scan. In group A (26 patients) gallium scan was performed within 7 days after surgery, in group B (8 patients) between 8 and 14 days after surgery, and in group C (8 patients) between 15 and 40 days after surgery. Our data showed that in group A, 61.5% had gallium accumulation at the surgical incision site. In group B, 50% had accumulation of gallium at the surgical incision site, while in group C only one patient (12.5%) showed gallium uptake. It is concluded that the incidence of increased gallium uptake at clean surgical incision sites is high after colorectal surgery. Nuclear medicine physicians should bear in mind the high incidence of non-specific gallium uptake at such sites during the interpretation of possible wound infection in patients after colorectal surgery.

Adolescent↗

PubMed2000

Does bowel preparation improve the quality of abdominal gallium scintigraphy?

Physiological accumulation of gallium in the intestine is a major weakness of gallium scintigraphy in evaluating the abdomen. In this study, we used two different cathartics to evaluate the efficacy of bowel cleansing in improving the quality of abdominal gallium imaging. One hundred and fifty patients underwent gallium scintigraphy and were randomly divided into three groups. Group A received no bowel preparation, Group B received 30 ml of castor oil the night before imaging, and Group C received bisacodyl the night before imaging. Gallium activity in the intestine was rated on a three-point scale from 0 to II based on the anterior view of a delayed 48-h gallium image. Our data showed that the incidence of gallium accumulation in the small intestine was low. On the contrary, there was high prevalence of gallium activity in the colon. Forty-eight percent of Group A patients had obvious gallium activity in the colon. The percentage decreased significantly to 28% and 22% in Groups B and C, respectively. No significant difference was noted between Group B and Group C. In conclusion, our data suggest that the application of either castor oil or bisacodyl significantly improves the quality of 48-h abdominal gallium scintigraphy. There were no significant differences in the efficacy of bowel cleansing on gallium activity between these two laxatives.

Abdomen↗

PubMed1988

Effect of gallium on bone mineral properties.

Gallium nitrate is biologically active in blocking bone resorption in vitro as well as in vivo. Administration of gallium nitrate to growing rats results in a dose-dependent accumulation of low levels of gallium in bone that is associated with specific changes in the mineral properties of bone. To elucidate in greater detail the changes induced by gallium, the properties of whole and density-fractionated bone samples from control and gallium-treated rats were examined. These studies showed that short-term treatment with gallium nitrate caused an increase in bone calcium and phosphate content. Devitalized bone powder from the gallium-treated rats was less soluble in acetate buffer and less readily resorbed by monocytes. Density fractionation analyses demonstrated that the largest proportion (76% by weight) of powdered metaphyseal bone particles from rats had a density of less than 2.15 g/cc. Following short-term treatment (14 days) with gallium nitrate (45 mg/kg body weight), a significant increase in the relative proportion of more dense bone (greater than or equal to 2.15 g/cc) was observed (24% for the control vs. 39% for the gallium-treated rats, P less than 0.01). In the diaphyseal samples, the largest proportion (88% by weight) of the bone powder had a density of greater than or equal to 2.15 g/cc. After short-term treatment with gallium, a slight decrease in mean diaphyseal particle density was observed. Measurement of calcium accretion with 45Ca in the gallium-treated rats demonstrated increased specific activity in the metaphyseal bone samples, densities = 2.0, 2.1, 2.15, and 2.25 g/cc; the difference was significant only for the 2.25 g/cc fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2001

Hodgkin's disease: prognostic role of gallium scintigraphy after chemotherapy.

Evaluation of the response to therapy is important for optimal selection of treatment strategy in patients with Hodgkin's disease (HD). Refractory disease requires intensive high-dose chemotherapy, whereas unnecessary treatment should be avoided in patients in complete remission. The purpose of this study was to evaluate the contribution of gallium-67 scintigraphy in predicting the clinical outcome in patients with HD and mediastinal involvement on the basis of scan results at the end of chemotherapy. Seventy-four patients with HD and mediastinal involvement were retrospectively investigated with 67Ga scintigraphy 72 h after injection of 220 MBq 67Ga citrate (planar and single-photon emission tomographic studies) following the completion of chemotherapy. At the same time, they all underwent computed tomography (CT). Patients were followed up for an average of 63 months (range 28-124 months). The disease status was newly diagnosed disease in 64 of the patients and relapse in 10. Systemic symptoms were absent (A) in 34 cases and present (B) in 40 cases. Forty-one patients had stage I or II disease and 33 patients had stage III or IV disease. Twenty-two patients had bulky disease on initial diagnosis. At the end of chemotherapy, all 74 patients showed regression of the mass by more than 50% (50%-100%) on CT. Patients were divided into two groups according to the positivity or negativity of the gallium scan after chemotherapy: 61 patients had negative and 13 patients had positive gallium scans. In the gallium-negative group, 19.7% of the patients relapsed and 91.8% were alive at the end of the follow-up. Relapse occurred in 20% of the patients with residual mass and in 19.6% of the patients without residual mass. In the gallium-positive group, 84.6% of the patients had recurrent disease and 61.5% were alive after intensive chemotherapy. There was a statistically significant difference in overall survival between patients with positive and patients with negative gallium results (P=0.0034). Disease-free survival differed significantly between patients with positive and patients with negative gallium scans at the end of chemotherapy (P<0.0001). The relative risk of death was 5.2 and the relative risk of relapse was 11.3 for patients with positive gallium scans, in comparison to those with negative gallium scans. The positive and negative predictive values for predicting relapse were 85% and 87%, respectively. It is concluded that even if gallium scan is performed at the end of chemotherapy, it can predict outcome. Alternative therapy may be required on the basis of gallium scan results obtained after treatment.

Adolescent↗

PubMed1997

Resistance to the antitumor agent gallium nitrate in human leukemic cells is associated with decreased gallium/iron uptake, increased activity of iron regulatory protein-1, and decreased ferritin production.

The mechanism of drug resistance to gallium nitrate is not known. Since gallium can be incorporated into ferritin, an iron storage protein that protects cells from iron toxicity, we investigated whether ferritin expression was altered in gallium-resistant (R) CCRF-CEM cells. We found that the ferritin content of R cells was decreased, while heavy chain ferritin mRNA levels and iron regulatory protein-1 (IRP-1) RNA binding activity were increased. IRP-1 protein levels were similar in gallium-sensitive (S) and R cells, indicating that R cells contain a greater proportion of IRP-1 in a high affinity mRNA binding state. 59Fe uptake and transferrin receptor expression were decreased in R cells. In both S and R cells, gallium inhibited cellular 59Fe uptake, increased ferritin mRNA and protein, and decreased IRP-1 binding activity. Gallium uptake by R cells was markedly diminished; however, the sensitivity of R cells to gallium could be restored by increasing their uptake of gallium with excess transferrin. Our results suggest that R cells have developed resistance to gallium by down-regulating their uptake of gallium. In parallel, iron uptake by R cells is also decreased, leading to changes in iron homeostasis. Furthermore, since gallium has divergent effects on iron uptake and ferritin synthesis, its action may also include a direct effect on ferritin mRNA induction and IRP-1 activity.

Antineoplastic Agents↗