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The influence of iron and gallium carriers on the in vitro and in vivo uptake of 67Ga and 59Fe by tumor cells has been studied. The results appear to indicate that ferritin might be involved in most of the systemic accumulation of 67Ga but that the mechanism of tumor uptake might be different.
Deferoxamine mesylate (DFO), given to rabbits 20 min after gallium-67 citrate, induces prompt and rapid urinary excretion of Ga-67 activity with concommitant decrease in blood and muscle activity. When DFO is given after 2 hr or later, the effect is smaller (15% decrease in blood activity compared with 50%). In abscess-bearing rats the same effect was observed: DFO accelerated the Ga-67 blood clearance by increasing urinary excretion. Tissue-distribution studies and direct counting of abscesses showed that DFO lowers Ga-67 activity in all organs as well as in the abscess if given 2 or 4 hr after Ga-67 citrate, but the abscess-to-blood ratio increases. At 24 hr after Ga-67 citrate, DFO administration causes an improvement in the ratios of abscess-to-blood and abscess-to-normal tissue. Thus, DFO could be used to decrease the radiation burden from Ga-67 citrate after imaging has been performed, and also to increase the target-to-nontarget ratio.
Gallium citrate scanning at 6 hr was used to evaluate a patient with active ulcerative colitis. The localization of 67Ga in the colon correlated with the extent of the inflammatory process. When either colonoscopy or radiographic contrast studies are contraindicated, 67Ga scanning at 6 hr may prove useful in the evaluation of active inflammatory bowel disease.
UNLABELLED: Metal chelate ions are commonly used in medical diagnostic imaging as MRI contrast or imaging agents. The efficacy of these metals depends on their in vivo behavior, which in turn depends on their in vivo speciation. METHODS: A computer model has been used to simulate the speciation of Ga3+ and Gd3+ in blood plasma. The model has been tested against known clinical data and then used to investigate Ga3+ uptake by tumor cells. The iatrogenic effect of a gadopentetic acid enhanced MRI scan upon the biodistribution of 67Ga citrate has also been calculated. RESULTS: The speciation of Ga3+ calculated using the computer model is concordant with clinical data. The results support transferrin mediated uptake of Ga3+ by tumor cells but also account for Ga(III) biodistribution observed in hypotransferrinemic subjects. In a study of the effect of gadopentetic acid upon 67Ga gallium citrate, neither residual DTPA nor [Gd(DTPA)]2- cause significant changes in the speciation of Ga(III). The calculations show that dissociation of 4% of the administered gadopentetic acid results in the formation of a mixed, Gd(III) and Ga(III), metal transferrin complex and a 100-fold increase in the concentration of [Ga(OH)4]-. CONCLUSION: Computer simulation is a valuable tool which can be used to explain/understand in vivo behavior of radioactive metal ions.
When gallium is injected into a patient who has received many transfusions, the resultant scan appears similar to a bone scan with renal excretion. This case report presents a 51-year-old man with myelofibrosis and myeloid metaplasia. Gullium-67 and 52Fe scans with 99mTc-pyrophosphate bone scintigrams are included.
Cytomegalovirus (CMV) infeciton is a frequent complication during the first few months following renal transplantation. The diagnosis is sometimes difficult but may be made by viral culture, a fourfold rise in the CMV antibody titer, or by demonstration of the CMV inclusions in the affected tissue. An increased pulmonary uptake of galliulm citrate Ga 67 has been demonstrated following renal transplantation in two patients, each of whom had a fourfold rise in CMV complement fixing antibody titer, one of whom additionally had CMV inclusion bodies in a lung biopsy specimen prior to clinical or radiological demonstration of the pulmonary involvement. Gallium imaging, therefore, appears to be a valuable noninvasive test for early diagnosis of CMV pulmonary infections.
The diagnostic accuracy of abdominal ultrasonography followed by gallium (Ga)-67 scintigraphy in 21 patients, aged 1 to 14 years, appearing with abdominal non-Hodgkin's lymphoma (NHL) was analyzed. All cases were confirmed by biopsy; in a majority (16 patients), the tissue was obtained from an abdominal mass at the time of laparotomy subsequent to the imaging studies. Nineteen satisfactory abdominal ultrasound examinations were performed; 18 were interpreted as characteristic of NHL. Sixteen of these were of masses involving the gastrointestinal tract. All 21 patients had 67Ga scintigraphy that demonstrated abnormal radionuclide accumulation in the abdomen. In no instance was the final diagnosis different from the one predicted by the combined imaging studies. Ultrasonography is recommended as the initial test in the evaluation of clinical presentations consistent with abdominal NHL to expedite suitable management and prevent inappropriate surgery.
Chronic osteomyelitis producing unexplained fevers without localizing symptomatology may present difficulty in detection and differentiation in patients with leukemia. Gallium citrate Ga 67 scintigraphy offers a method of detection and localization of both the osseous and extraosseous manifestations of such a process. Once identified, further evaluation by conventional radiographic or sectional imaging techniques may further define the process. We describe three patients with leukemia and unexplained fever in whom occult chronic osteomyelitis was diagnosed by 67Ga scintigraphy, which offers an ideal screening procedure and should be utilized in this clinical setting.
A total of 92 lymphangiograms (L.G.) and gallium scans (G.S.) done in 51 patients with non-Hodgkin's lymphoma were evaluated to assess their usefulness in detecting infradiaphragmatic disease. It was found that the correlation between both procedures was fairly good before treatment (85%) but decreased considerably after therapy. A significant number of patients persistently had positive L.G. after treatment, with a negative G.S. No histologic examination of tissues was performed, however, to confirm the radiographic findings. A higher number of equivocal G.S. were found both before and after treatment. No significant difference in correlation was found between the histiocytic and lymphocytic lymphomas but the former were found to have a striking frequency of negative L.G. and G.S. in the infradiaphragmatic area.
In 37 patients with seemingly localized non-Hodgkin's lymphoma of the Waldeyer's ring (WR-NHL), lymphangiography (LAG) and/or gallium-67 scans (Ga-67 scans) were done. Before these procedures, 20 patients were diagnosed as Stage I, and 17 as Stage II. LAG was done for 30, and Ga-67 scans for 32, 25 of whom had both. Five patients (16%) were upstaged to Stage III or IV by Ga-67 scans. Only one (3%) had abnormal LAG findings, in whom Ga-67 scans also showed abnormal accumulation in the para-aortic region. Because of this low positive rate, LAG is not recommended for staging of WR-NHL.
The value of gallium 67 (Ga) imaging in monitoring lymphoma response to treatment was assessed in 25 patients with Ga-avid tumors and compared to body computed tomography (CT), chest radiographs, and palpation of tumor infiltrated peripheral lymph nodes. Ga imaging was negative in 95% (20/21) of the patients who were clinically considered to be in remission and in whom treatment was stopped. The disease did not recur during a follow-up of 12 to 26 months in 15 patients. Six patients developed recurrence of the disease 3 to 12 months after treatment was stopped. In all six patients Ga imaging became positive again at the time of the appearance of active disease. In the group of patients in remission, CT was negative in 57% (11/19), chest x-rays in 55% (6/11) and peripheral lymph nodes were palpated in none of the patients (13/13). In four patients that did not achieve remission after treatment, Ga scans were positive. Ga imaging appears useful in monitoring lymphoma response to treatment. This is probably because Ga imaging monitors tumor cell viability, whereas body CT and chest radiographs show the tumor mass, which may consist of fibrotic or necrotic tissue.
This article presents the case of a 22-year-old patient with treated Hodgkin disease (HD) who had mediastinal widening on computed tomography scan after chemotherapy. This mass was gallium avid. These findings were explained by histologically documented benign thymic hyperplasia, the first such case reported in an adult with HD, to the knowledge of the authors. The literature on thymic hyperplasia after chemotherapy is reviewed.
OBJECTIVE: To evaluate gallium-67 (67Ga) uptake and the value of 67Ga scintigraphy for diagnosis of macrophagic myofasciitis (MMF), a recently identified inflammatory myopathy. METHODS: Twelve consecutive patients with MMF confirmed by muscle biopsy, 10 with polymyositis, 10 with sarcoidosis, 8 with fibromyalgia, and 10 with lymphoma without muscle symptoms (serving as normal controls for muscle) were included. Patients received 1.8 MBq 67Ga per kg body weight by intravenous injection, and scintigraphy was performed with a 2-head gamma camera. The various views were acquired for the 3 main photopeaks of 67Ga 48 hours after infusion, and were analyzed in 2 blinded experiments by nuclear physicians. A semiquantitative scale was used to compare the uptake of 67Ga in the vascular soft tissue background with that in the muscles or joints of MMF patients, and with that in the normal controls. RESULTS: The MMF patients (4 men and 8 women, mean +/- SD age 47.8 +/- 8.7 years) had chronic myalgia (n = 11; predominantly in the lower limbs), asthenia (n = 10), arthralgia (n = 7), mild muscle weakness (n = 5), and high serum creatine kinase levels (n = 6). All MMF patients had significantly higher levels of 67Ga uptake in the muscle and para-articular areas than that recorded for the soft tissue background and for the controls. Muscle uptake was bilateral, symmetric, and homogeneous, and predominantly localized in the legs. No linear enhancement corresponding to fascias or synovial involvement was observed. In patients with polymyositis, symmetric, but heterogeneous, 67Ga uptake was observed in muscle, but not in the fascia. In patients with sarcoidosis, 67Ga uptake was nodular and heterogeneous in muscle, was not detected in the fascia, and was suggestive of synovial involvement in the joints. The uptake of 67Ga in fibromyalgic patients was similar to that in normal controls and to that in the soft tissue background. CONCLUSION: MMF is a new condition involving characteristic changes that can be detected by deltoid muscle biopsy. It usually manifests as a weakly specific, chronic arthromyalgic syndrome that predominates in the lower limbs. 67Ga scintigraphy is a noninvasive method that may make it easier to differentiate MMF from fibromyalgia and sarcoidosis.
Tumor cells of 14 cases of non-Hodgkin lymphomas and 2 cases of Hodgkin disease were tested for the presence of the transferrin receptor (CD71) by flow cytofluorimetry before 67gallium imaging. It appeared that expression of CD71 phenotype was closely related to the positivity of gallium scan before therapy. We feel that this test is able to predict the avidity for 67gallium and the clinical implications are discussed.
Gallium arsenide (GaAs) inhibited, dose dependently, delta-aminolevulinic acid dehydratase (ALAD) activity in blood (as observed on days 1, 7 and 15), liver and brain (on day 15) after a single oral treatment. Levels of blood zinc protoporphyrin (ZPP) and urinary delta-aminolevulinic acid (ALA) excretion were elevated on day 7 and day 15 following exposure to 2000 mg kg-1 GaAs. A dose-dependent increase in blood As contents was observed while blood Ga was detectable only at higher doses.
Gallium nitrate (GN) is an agent used in the treatment of hypercalcemia. To more fully characterize the direct actions of GN on bone, we examined its effects on medium calcium, medium beta-glucuronidase (beta-GLU), and collagen synthesis in control and hormone-stimulated neonatal (4-6 days) mouse calvariae in vitro. GN (10 micrograms/ml) inhibited parathyroid hormone-stimulated (PTH; 1 nM) calcium release. A 24 h preincubation with 10 micrograms/ml of GN was required for complete inhibition; partial inhibition was seen with 12 h preincubation; 1, 3, or 6 h was inadequate. A dose-response study showed that with 24 h preincubation, 5, 3, and 1 microgram/ml of GN inhibited 81, 62, and 0% of PTH-induced calcium release. The effects of GN on the release of beta-GLU generally paralleled those on the release of calcium except that 10 micrograms/ml of GN stimulated beta-GLU release. Collagen synthesis was inhibited 50% by 3 micrograms/ml of GN, whereas noncollagen protein synthesis was unaffected. With PTH + GN no further decrease was observed. When GN was withdrawn from the medium after 24 h of preincubation, the inhibitory effect on calcium release and beta-GLU activity, but not on collagen synthesis, persisted through the 72 h of culture. GN also inhibited the resorption elicited by thyroxine (1 microM) and interleukin-1 beta (10 nM) but not by 1,25-dihydroxyvitamin D3 (30 pM). Our results indicate that GN is a powerful inhibitor of bone resorption in neonatal mouse calvariae even at low doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Gallium nitrate (GN) is an inhibitor of bone resorption and thereby may result in a change in coupled bone formation. In the present investigation the effects of GN on bone formation were studied in the rat osteosarcoma (ROS) 17/2.8 cell line and normal diploid rat osteoblasts (ROB) in vitro and the femur of rats treated in vivo, measuring mRNA levels for two osteoblast parameters, type I collagen, a marker of matrix formation, and osteocalcin, a bone specific protein and also histone H4, a marker of cell proliferation. GN, at 50 microM for 3 h, increased type I collagen mRNA levels by 132% in ROS 17/2.8 cells and by 122% in proliferating ROB cells. Osteocalcin (OC) mRNA levels were decreased by 61% in ROS 17/2.8 cells and by 97% in differentiated ROB cells. These changes occurred in the absence of any effects on cell proliferation. Seventy-day-old female rats were then treated with GN, 0.5 mg/kg/day, for 3 weeks. As previously reported, GN decreased serum calcium levels, but had no effect on lumbar or femoral bone density. In contrast to the in vitro effects, GN had no effect on type I collagen steady-state mRNA levels in the femur; however, it decreased OC steady-state mRNA levels in the femur by 58%. These results suggest that GN has similar in vitro effects in transformed and normal osteoblasts, while the collagen-stimulatory effects observed in vitro cannot be extrapolated to in vivo models. The consistent inhibition of osteocalcin in vitro and in vivo suggests a more specific target for GN that may relate to its effects in inhibiting bone resorption in normal rats.
BACKGROUND AND OBJECTIVE: In this study, the effect of low energy Gallium arsenide (GaAs) laser irradiation on the compound action potential of frog gastrocnemius muscle were investigated. STUDY DESIGN/MATERIALS AND METHODS: Sixty frogs were divided into different six dose groups: laser 1 (1 Hz), laser 2 ( 4 Hz), laser 3 (16 Hz), laser 4 (64 Hz), laser 5 (128 Hz), and laser 6 (1,000 Hz, DC, continue) (in each group n=10). Low energy GaAs laser (wavelenght: 904 nm, pulsed duration: 220 nanoseconds, peak power per pulse: 27 W, total applied energy density: 0.001-25.7 J/cm2) was used for the experiment. Compound muscle action potentials were recorded before laser irradiation and these data were accepted as control group. After recording the control data, each muscle was irradiated by the laser. Action potentials were recorded at 1, 5, 10, 15, and 20 minutes of irradiation time in each group by using standartized needle electromyography and nerve conduction study techniques. Distal motor latency, peak to peak amplitude, area, and total duration of action potential were measured. Repeated measures analysis of variance were used for the statistical evaluation. RESULTS: No significant differences were detected between control and laser dose groups in muscle action potential parameters. CONCLUSIONS: This study revealed that at the different repetition rate and exposure time, low energy GaAs laser does not have any significant effect on frog gastrocnemius action potential.