Gallium-67 scintigraphy in malignant melanoma.
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The syndrome of opsoclonus and myoclonus may be the first presenting symptom of neuroblastoma. The disorder is often controlled by treatment with adrenocorticotropic hormone (ACTH). A child with this disorder and treated with ACTH gel had abnormal uptake of 67Ga in both adrenal glands during studies to attempt to detect an occult neuroblastoma. Repeat 67Ga scans proved to be normal once the ACTH was discontinued and the patient was treated with prednisone. It is concluded that ACTH stimulation of normal adrenal tissue was responsible for these abnormal findings.
In order to assess the utility of 67gallium citrate in delineating malignant pleural mesothelioma from benign asbestos-related pleural disease, 49 patients with malignant mesothelioma and 16 with benign asbestos-related pleural disease were studied. Seven patients with malignant mesothelioma had no history of asbestos exposure, while the remaining 58 patients were exposed. Forty-three of the 49 patients (88%) with malignant mesothelioma had a positive 67gallium scan including 36 of the 42 (86%) patients with asbestos exposure and all 7 patients without a history of asbestos exposure. Three of 16 patients (19%) with benign asbestos-related pleural disease had a positive scan. 67Gallium radionuclide imaging is nonspecific but may be valuable in noninvasive monitoring of asbestos-exposed populations, which have a high risk for the late development of benign and/or malignant pleural disease.
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Somatostatin analogs labeled with radionuclides are of considerable interest in the diagnosis and therapy of SSTR-expressing tumors, such as gastroenteropancreatic, small cell lung, breast and frequently nervous system tumors. In view of the favorable physical characteristics of the Ga isotopes (67)Ga and (68)Ga, enabling conventional tumor scintigraphy, PET and possibly internal radiotherapy, we focused on the development of a Ga-labeled somatostatin analog suitable for targeting SSTR-expressing tumors. For this purpose, 3 somatostatin analogs, OC, TOC and TATE were conjugated to the metal chelator DOTA and labeled with the radiometals (111)In, (90)Y and (67)Ga. They were then evaluated for their performance in the AR4-2J pancreatic tumor model by testing SSTR2-binding affinity, internalization/externalization in isolated cells and biodistribution in tumor-bearing nude mice. Surprisingly, we found that, compared to (111)In or (90)Y, labeling with (67)Ga considerably improved the biologic performance of the tested somatostatin analogs with respect to SSTR2 affinity and tissue distribution. (67)Ga-labeled DOTA-somatostatin analogs were rapidly excreted from nontarget tissues, leading to excellent tumor-to-nontarget tissue uptake ratios. Of interest for radiotherapeutic application, [(67)Ga]DOTATOC was strongly internalized by AR4-2J cells. Furthermore, our results suggest a link between the radioligand charge and its kidney retention. The excellent tumor selectivity of Ga-DOTA somatostatin analogs together with the different applications of Ga in nuclear oncology suggests that Ga-DOTA somatostatin analogs will become an important tool in the management of SSTR-positive tumors.
To evaluate the inhalation toxicity of Ga2O3, F344 rats were exposed nose-only to 0.2 micron Ga2O3 particles 2 h/day, 5 days/week for 4 weeks. The exposure concentration was 23 +/- 5 mg/m3 (mean +/- SD) resulting in lung burdens of 0.8 +/- 0.1 mg Ga2O3/lung (mean +/- SE) at the end of 4 weeks of exposure. Analysis of bronchoalveolar lavage fluid of exposed rats showed marked responses. One day after termination of exposure, lactate dehydrogenase was increased 6-fold, and the lysosomal enzyme, beta-glucuronidase, was increased 38-fold in rats exposed to Ga2O3 compared to sham exposed controls. Alkaline phosphatase, glutathione reductase, glutathione peroxidase, white blood cells, acid proteinase, and protein were increased 3- to 4-fold. Responses remained elevated 6 and 12 months after exposure. Lung clearance of radiolabeled tracer particles was evaluated 4 days and 6 months after the end of 4 weeks of Ga2O3 exposures. Long-term clearance half-times were significantly longer (3-4 fold, P less than 0.01) in rats exposed to Ga2O3 than in the sham-exposed control rats at both 4 days and 6 months, indicating persistent impairment of particle clearance. Histopathological lesions consisted primarily of alveolar proteinosis 1 day after 4 weeks exposure, progressing in severity to large focal lesions of alveolar histiocytosis and septal fibrosis 6 and 12 months after exposure. Inhaled Ga2O3 produced cytotoxic, inflammatory, and fibrogenic responses of comparable or greater magnitude than those seen after similar exposures of rats to inhaled quartz particles in other studies. These data show that inhaled Ga2O3 particles produce considerable toxicity and exposures in the work place should be limited.
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Studies on the distribution of 67Ga in pregnant rabbits showed a marked concentration of the isotope in uterine tissue and flushings of 5-day pregnant rabbits 24 hours after isotope injection. The isotope no longer localized throughout the uterine tissues and flushings on injection of 7- to 8-day pregnant rabbits but was specifically associated with the blastocysts and sites of implantation. As the gestation time progressed 67Ga increasingly concentrated in placental and mammary tissue while the concentration in serum and thymus tissue decreased. The marked concentration in placental tissue was readily discernible on total-body scans of pregnant rabbits. Column chromatography of uterine washings and placental extracts from pregnant rabbits and thymus extracts from estrous rabbits showed most of the isotope associated with moieties greater than or equal to 200,000 MW whereas the isotope in "milk" and extracts of mammary tissue was bound to components of 25,000-35,000 MW. Extracts of thymus from pregnant rats showed a marked, selective loss of 67Ga binding in two peaks of approximately 50,000 and 120,000 MW compared to the chromatographic profile of extracts from normal rat thymus.
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BACKGROUND AND OBJECTIVE: The present study is aimed to describe short-term results on selected microbiological and clinical parameters obtained by treatment with soft laser in conjunction with methylene blue and/or mechanical subgingival debridement in human periodontal disease. STUDY DESIGN/MATERIALS AND METHODS: Ten patients, in whom each dental quadrant was randomly designated to receive one of four types of treatment procedures, were included in the study. Groups of quadrants received: scaling/root planing (SRP); laser application (L); SRP combined with L (SRP/L); oral hygiene instructions (OHI). Four single rooted teeth (one in each quadrant), having an interproximal site with a probing depth of 4 mm mesio-buccally, were selected in each patient. The selected teeth were first assessed for microbiological (one site/tooth) and then for clinical variables (six sites/tooth). Supragingival irrigation with methylene blue was performed prior to laser application. The microbiological (proportions of obligate anaerobes) and clinical measurements (plaque and gingival indices, bleeding on probing, probing pocket depth) were evaluated over a period of 32 days. RESULTS: Only the SRP/L and SRP groups provided significant reductions in the proportions of obligate anaerobes before and after treatments with no significant differences in between. Parallel to the microbiological changes, both SRP/L and SRP resulted in similar clinical improvements, whereas L alone revealed a limited effect similar to OHI. CONCLUSION: Within the limits of this study, methylene blue/soft laser therapy provided no additional microbiological and clinical benefits over conventional mechanical debridement.
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