indium-oxine and Hodgkin-Disease

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

Untreated patients with Hodgkin's disease (HD) have a blood T-lymphocytopenia mainly caused by a reduction of the CD4+ subset. Indirect support for a sequestration of T cells in the spleen and tumor-involved lymphoid tissue has accumulated. To test the hypothesis that the blood CD4 T-lymphocytopenia in patients with HD is caused by an altered lymphocyte traffic, 12 untreated HD patients and five in complete clinical remission (CCR) were studied. Blood lymphocytes were collected by leukapheresis and gradient centrifugation, and were further purified by an adherence step. The cells were labeled with indium-111 oxine and reinfused intravenously into the patient. The radioactivity of CD4+ and CD8+ blood lymphocytes separated by immunoabsorption was measured from serial blood samples. CD4+ cells were eliminated more rapidly in untreated patients than patients in CCR. Repeated gamma camera imaging after autotransfusion of indium-111 oxine labeled cells demonstrated an accumulation of radioactivity in tumor-involved tissue of untreated patients. These findings support the concept of an enhanced elimination of CD4+ cells in patients with active HD that may contribute to the observed blood T-lymphocytopenia and may reflect a biologic response to the tumor.

Topics: Adolescent; Adult; Aged; Antigens, Differentiation, T-Lymphocyte; CD4-Positive T-Lymphocytes; CD8 Antigens; Female; Hodgkin Disease; Humans; Hydroxyquinolines; Indium Radioisotopes; Lymphocyte Depletion; Male; Metabolic Clearance Rate; Middle Aged; Organometallic Compounds; Oxyquinoline; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

The present study was designed to investigate the survival of platelets of differing densities in normal and post-splenectomized subjects. Autologous platelets, labelled with 111In-oxine, were reinjected into normal subjects (n = 12); 63% were recovered in the circulation and their survival curve was linear with a T 1/2 of 4.5 d. When the platelets were layered onto a continuous Percoll gradient, they formed a band extending between 1.040 and 1.080 g ml-1. After fractionation of the gradient the specific radioactivity of 111In platelets recovered was measured. The specific activity of low density platelets (average 1.050 g ml-1) decreased rapidly with a T 1/2 of 2.0 d, whilst medium density platelets (average 1.060 g ml-1) survived with a T 1/2 of 4.5 d; high density platelets (average 1.073 g ml-1) exhibited a T 1/2 greater than 5.0 d. This latter population of high density platelets also showed a significant increase in specific activity on the first day following injection. In post-splenectomy subjects a similar relationship between density and 111In associated activity was observed but no increase in the specific activity of the dense platelets on day 1 was observed. We conclude that high density autologous 111In-platelets are preferentially retained in the spleen and have a more prolonged survival than those of lower density.

Topics: Adult; Blood Platelets; Cell Survival; Centrifugation, Density Gradient; Hodgkin Disease; Humans; Indium; Male; Middle Aged; Organometallic Compounds; Oxyquinoline; Postoperative Period; Radioisotopes; Splenectomy

The in vitro use of the radioisotope indium 111 (111In) was examined as a radiolabel for lymphocytes obtained from both normal individuals and patients with a variety of lymphoid malignancies. Successful cell labeling requires a chelator. The traditional agent oxine, has proved to be toxic to the lymphoid lineage. Cellular uptake of 111In mediated by the chelator oxine was compared with that of a new chelator, tropolone. Oxine provided better labeling efficiency (48%) than tropolone (35%) for the labeling of normal lymphocytes. By contrast, lymphocytes from patients with chronic lymphocytic leukemia had a nearly twofold greater labeling efficiency when tropolone was substituted for oxine. Further studies demonstrated that tropolone induced functional injury to lymphocytes when mitogenic response to concanavalin A, pokeweed mitogen, and phytohemagglutinin was assessed. Similar toxicity was found when tropolone was compared with oxine. In addition, tropolone produced damaging structural changes seen by both scanning and transmission electron microscopic examination. These changes were both variable and not predictable. Shortening of the incubation time of the chelator with the cell provided the least amount of cellular injury. These findings suggest that tropolone be used as an alternative mediator of lymphocyte labeling with 111In only under critically defined conditions.

Topics: Cells, Cultured; Cycloheptanes; Hodgkin Disease; Humans; Hydroxyquinolines; Indium; Leukemia; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Lymphoma; Microscopy, Electron; Microscopy, Electron, Scanning; Organometallic Compounds; Oxyquinoline; Tropolone