Gallium disrupts iron metabolism of mycobacteria residing within human macrophages.
Mycobacterium tuberculosis and M. avium complex (MAC) enter and multiply within monocytes and macrophages in phagosomes. In vitro growth studies using standard culture media indicate that siderophore-mediated iron (Fe) acquisition plays a critical role in the growth and metabolism of both M. tuberculosis and MAC. However, the applicability of such studies to conditions within the macrophage phagosome is unclear, due in part to the absence of experimental means to inhibit such a process. Based on the ability of gallium (Ga(3+)) to concentrate within mononuclear phagocytes and on evidence that Ga disrupts cellular Fe-dependent metabolic pathways by substituting for Fe(3+) and failing to undergo redox cycling, we hypothesized that Ga could disrupt Fe acquisition and Fe-dependent metabolic pathways of mycobacteria. We find that Ga(NO(3))(3) and Ga-transferrin produce an Fe-reversible concentration-dependent growth inhibition of M. tuberculosis strains and MAC grown extracellularly and within human macrophages. Ga is bactericidal for M. tuberculosis growing extracellularly and within macrophages. Finally, we provide evidence that exogenously added Fe is acquired by intraphagosomal M. tuberculosis and that Ga inhibits this Fe acquisition. Thus, Ga(NO(3))(3) disruption of mycobacterial Fe metabolism may serve as an experimental means to study the mechanism of Fe acquisition by intracellular mycobacteria and the role of Fe in intracellular survival. Furthermore, given the inability of biological systems to discriminate between Ga and Fe, this approach could have broad applicability to the study of Fe metabolism of other intracellular pathogens. (+info)
67Gallium in 68 consecutive infection searches.
When employed in the study of peripheral infections, 67Ga scanning is sensitive and accurate. When used as a diagnostic tool for suspected abdominal abscesses, it locates and delineates abscesses in somewhat over half the cases. Moreover, the true-negative rate is high and the false-positive rate is acceptably low. Gallium scans should be interpreted with all available clinical information. The coexistence of noeplasm is a problem which at present is not completely resolved. (+info)
Three-dimensional reconstruction of lung perfusion image with positron detection.
Transverse section images of the distribution of pulmonary perfusion in a canine have been obtained using microspheres labeled with the positron-emitting isotope 68Ga and a three-dimensional reconstruction technique. The reconstruction method is more accurate than conventional tomographic procedures and is facilitated by the use of positron detection. The transverse sections presented demonstrate the capacity of the technique to delineate reduction in regional perfusion resulting from occlusion of the artery to the left lower lobe. (+info)
Gallium gallbladder scanning in cholecystitis.
Gallium has been shown to accumulate in metabolically active tissue including sites of infection. The purpose of this study was to evaluate gallium scanning in cholecystitis. Ten patients with cholecystitis were studied using conventional gallium scanning techniques. Five patients with acute cholecystitis showed intense gallium accumulation in the gallbladder area. One of five patients with chronic cholecystitis showed significant accumulation in the gallbladder. The limitations of this method are mainly the need for serial scanning to rule out gallium accumulation in the hepatic flexure of the colon and also the failure to detect consistently a chronically diseased fibrotic gallbladder. We conclude that gallium scanning of the gallbladder is an important adjunctive study in the evaluation of cholecystitis. (+info)
Diminished uptake of 67Ga-citrate in a case of pseudarthrosis.
A 22-year-old man with pseudarthrosis and infection of the right hip was referred for a 67Ga-citrate scan. A striking decrease was seen in normal bone and soft-tissue uptake in the entire right leg compared with the normal limb. Aortic injection of 99mTc-labeled microspheres showed increased trapping in the region of the hip but contrast angiography was unremarkable. Despite clinical imporvement, 67Ga uptake by the right leg on a repeat scan did not return to normal. This case represents the first report of a "photon-deficient" body part on 67Ga scanning. (+info)
Breast scintigraphy with 99mTc-pertechnetate and 67Ga-citrate.
Radionuclide breast scintigraphy was evaluated as a noninvasive tumor-localizing modality. Technetium-99m-pertechnetate (99mTcO4) demonstrated good correlation between malignancy and postive scintigraphy (88% accuracy in 16 cases of breast carcinoma). The high false-positive rate (29% of proven benign breast disease) limits the use of 99mTcO4 as an aid to differential diagnosis. Gallium-67-citrate (67Ga) is limited as a diagnostic adjunct (localizing in only five of ten breast malignancies). Refined techniques of positioning, shielding, gamma camera imaging, and computer assistance have helped in visualizing abnormal radionuclide accumulation. (+info)
Clinical value of [(18)F]fluoro-deoxyglucose positron emission tomography for patients with fever of unknown origin.
We describe the diagnostic contribution of [(18)F]fluoro-deoxyglucose (FDG) positron emission tomography (PET) scan in 58 consecutive cases of fever of unknown origin (FUO) and compare this new approach with gallium scintigraphy. This investigation was performed from March 1996 through October 1998 at Gasthuisberg University Hospital in Leuven, Belgium. A final diagnosis was established for 38 patients (64%). Forty-six FDG-PET scans (79%) were abnormal; 24 of these abnormal scans (41% of the total number of scans) were considered helpful in diagnosis, and 22 (38% of the total number) were considered noncontributory to the diagnosis. In a subgroup of 40 patients (69%), both FDG-PET and gallium scintigraphy were performed. FDG-PET scan and gallium scintigraphy were normal in 23% and 33% of these cases, respectively; helpful in diagnosis in 35% and 25%, respectively; and noncontributory in 42% each. All foci of abnormal gallium accumulation were also detected by use of an FDG-PET scan. We conclude that FDG-PET is a valuable second-step technique in patients with FUO because it yielded diagnostic information in 41% of the patients in whom the probability of a definite diagnosis was only 64%. FDG-PET scan compares favorably with gallium scintigraphy for this indication. Because of the quick results (within hours instead of days), FDG-PET scan may replace gallium scintigraphy as a radiopharmaceutical for the evaluation of patients with FUO. (+info)
Uptake of 67Ga in the regenerating rat liver and its relationship to lysosomal enzyme activity.
The uptake of 67Ga citrate has been studied in the regenerating rat liver over a period up to 72 hr after partial hepatectomy. The concentration of 67Ga was found to be maximal (four times that of controls) 42 hr after hepatectomy. This was shown to be related to lysosomal enzyme activity rather than to specific phases of the cell cycle, there being a highly significant correlation (p smaller than 0.001) with aryl sulfatase activity. In both regenerating and normal rat livers, it was shown that 67Ga uptake is reduced when protein synthesis is inhibited by cycloheximide but is unaffected by inhibition of DNA synthesis by cytosine arabinoside. (+info)