indium-oxine and Lymphoma--Non-Hodgkin

The use of radioisotopes for cell labeling has been a major tool in hematology laboratory research. Chromium-51-labeling of hematologic cells and lymphocytes has been used for years to study the migration and sequestration of these cells in the spleen and other sites. The substantial recirculation of lymphocytes from blood into lymphoid tissue and back into blood is well described. Recently, new approaches for radiosotopic cell labeling have gained prominence in the investigation of various aspects of malignant diseases and in the clinical care of such patients. Isotopes such as indium-111 can be visualized with standard scanning techniques providing further information about the migration of normal and malignant cells has been discovered. In vivo studies have been performed with indium-111 in animals and humans, including comparisons of the migration of abnormal cells (malignant) and of lymphocytes to abnormal nodes. Evaluation and comparison of the migration of carcinoma cells, normal lymphoid cells, and malignant lymphoid cells in animals show markedly different patterns of distribution, which could have bearing on investigations of mechanisms of metastasis. In vivo human studies also have evaluated the migration patterns of lymphoid cells from patients with chronic lymphocytic leukemia and well-differentiated lymphoma, showing very different migrating behavior between these two polarities of a similar disease. These types of studies, while initially phenomenonologic, may provide a basis for a better understanding of these diseases. There are concerns about the use of an isotope such as indium-111 for the labeling of long-lived cells such as lymphocytes. Laboratory studies have demonstrated impaired cell function at high concentrations of radioactivity. Some workers have expressed concern about long-term changes in cells that recirculate. Others cite precedents of other long-term uses of isotopes, therapeutically, without detrimental effects. These concerns continue to be investigated. Finally, an area of much interest in the use of indium-111 is the labeling of granulocytes. This technique has been useful diagnostically, to localize infections. The major value in patients with malignancy, primarily with hematologic malignancies, is to evaluate the potential benefit of granulocyte transfusions. Many of these patients develop prolonged granulocytopenia and become infected, and granulocyte transfusions may become a therapeutic consideration.(ABSTRACT TRU

Topics: Agranulocytosis; Animals; Blood Transfusion; Cell Movement; Chromium Radioisotopes; Granulocytes; Hodgkin Disease; Humans; Indium; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphocytes; Lymphoma, Non-Hodgkin; Neoplasms; Organometallic Compounds; Oxyquinoline; Radioisotopes; Radionuclide Imaging; Rats; Sezary Syndrome

Indium-111-labeled-leukocyte scintigraphy was performed on three febrile patients, two of whom had no signs or symptoms referable to the respiratory tract. The third patient had dyspnea on exertion, unchanged over two months. Their past histories were remarkable in that all three had recently undergone chemotherapy for malignancy (2 lymphoma, 1 malignant thymoma). Diffuse pulmonary uptake of labeled leukocytes was observed in all three individuals. As a direct result of leukocyte imaging, all three underwent fiberoptic bronchoscopy and transbronchial biopsy. The final diagnosis in each of these patients was drug-induced pneumonitis, which responded to treatment with corticosteroids. This entity should be added to the group of conditions, both infectious and noninfectious, that cause diffuse pulmonary uptake on labeled leukocyte images. Moreover, in the appropriate clinical setting, even in the absence of pulmonary signs or symptoms, diffuse pulmonary uptake of labeled leukocytes should alert the physician to the possibility of drug-induced pneumonitis.

Topics: Aged; Antineoplastic Agents; Humans; Leukocytes; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Pneumonia; Radionuclide Imaging; Thymoma

It has shown that, after intravenous administration of autologous lymphocytes labelled with the beta-emitting radionuclide 114Inm, the cells initially migrate normally before succumbing to the toxic effects of the radiation. The radioactive material is then released from the cell and taken up by neighbouring radioresistant macrophages, thereby localizing a field of radiation to the site of lymphocyte death. Using this technique, lymphocytopoenia has been produced in rats. We have measured the whole-body distribution and excretion of radioactivity in patients who received escalating activities of 114Inm-labelled lymphocytes. All patients had active non-Hodgkin's lymphoma involving the spleen and liver which proved resistant to combination chemotherapy and conventional radiotherapy. Following intravenous administration, the labelled cells cleared rapidly from the vasculature with only 15% remaining in the peripheral blood at 30 min. The radioactivity continued to fall over the next 5 days to approximately 3% and was maintained at approximately 2% for up to 90 days. There was an almost immediate uptake of radioactivity by the spleen and liver which reached approximately 85% of the injected dose by 48 h. The localization of radioactivity stabilized by 48 h and thereafter the whole-body content fell by approximately 0.8% per day. Up to 5% of the administered radioactivity accumulated in the bone marrow. The activities administered were too low to produce a therapeutic response and no toxicity was experienced by the patients. A therapeutic study at higher activities is now underway.

Topics: Humans; Hydroxyquinolines; Indium Radioisotopes; Lymphocytes; Lymphoma, Non-Hodgkin; Organometallic Compounds; Oxyquinoline

The migration pattern of lymphocytes labelled with indium-111 was followed in a patient with B cell non-Hodgkin's lymphoma treated with a murine monoclonal anti-idiotype antibody. During the early phase of continuous infusion of antibody rapid fluxes of labelled lymphocytes into and out of the blood were seen. Dynamic scanning showed immediate uptake in the lungs; thereafter activity decreased in the lungs and increased in the liver. Studies of labelled and unlabelled cells in the circulation showed that treatment resulted in the removal of lymphocytes from the blood which was repopulated from an extravascular compartment. Tumour cells were shown to be cleared from the blood by the reticuloendothelial system in the liver. Indium-111 should be used circumspectly because it may cause chromosomal damage in labelled cells, but it is clearly useful as a radiolabel for following the migration pathways of lymphocytes in vivo.

Topics: Aged; Antibodies, Monoclonal; B-Lymphocytes; Cell Movement; Female; Humans; Hydroxyquinolines; Immunoglobulin Idiotypes; Indium; Leukocyte Count; Lymphocytes; Lymphoma, Non-Hodgkin; Organometallic Compounds; Oxyquinoline; Radioisotopes; Radionuclide Imaging; Time Factors