indium-oxine and Neoplasms

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

Radionuclide therapy remains a promising arsenal against cancer. However, low tumor uptake, high radiation dose to normal organs, and subsequent adverse effects are challenging problems. This study assessed the therapeutic significance of lipid-soluble compounds of (111)In, which passively diffuse through the cell membrane, bind to cytoplasmic components, and remain cell bound until decay.. Athymic nude mice bearing human colorectal, prostate, or breast cancer received 11.1-14.8 MBq (300-400 micro Ci) (111)In-8-hydroxyquinoline ((111)In-oxine) or (111)In-mercaptopyridine-N-oxide ((111)In-Merc) in 200 micro L solution intratumorally through a multihole needle. Tumors in some mice were dissected, and 20- micro m-thick sections were autoradiographed. In additional mice, tumor diameter was measured daily, mice were imaged and weighed, and blood samples were drawn for determination of neutrophil counts for up to 28 d after injection. Some mice were sacrificed at predetermined times for quantitative tissue distribution of (111)In. Additionally, tumor cells were labeled with (111)In-oxine and homogenized, and (111)In associated with cell components was determined using polyacrylamide gel electrophoresis. Radiation dose that could be delivered to adjacent tissues was estimated. The (111)In absorbed dose as a function of radial position r in a 1-g tumor was theoretically compared with those of beta-emitting radionuclides (90)Y and (177)Lu.. More than 85% of (111)In remained in tumors, bound to cell cytoplasmic components of apparent molecular weights 250 and 6 kDa. (111)In in tumors was uniformly distributed. Only 2% of the injected (111)In was in the liver, kidneys, and carcass. Statistical analysis showed that on day 28, control tumors grew >100%, whereas treated tumors either had growth arrest or grew only slowly (17%). The estimated radiation dose per megabecquerel (millicurie) injected was 90 Gy/g (9,000 rad/g), of which 64% was from conversion electrons, 16% from Auger electrons, 20% from gamma-photons and x-rays, respectively. Radiation dose to adjacent normal organs was 5%-10% of the radiation dose to the tumor and negligible to the liver and kidneys. Neutrophil counts remained unchanged. Mouse body weight was +/-10% of the initial weight. The radiation dosimetry for (111)In and (177)Lu compared favorably, but not that of (90)Y.. Treatment is independent of receptor density, heterogeneity, or the hypoxic status of cells. It is applicable to treat all known and accessible tumor types, and it delivers a negligible radiation dose to vital organs and only 5%-10% of the radiation dose to organs adjacent to the tumor. Intratumoral administration of (111)In-oxine appears to be a feasible, effective, safe, and promising treatment for cancer.

Topics: Animals; Breast Neoplasms; Cell Line; Colorectal Neoplasms; Dose-Response Relationship, Radiation; Drug Delivery Systems; Feasibility Studies; Humans; Injections, Intralesional; Lipids; Male; Mice; Mice, Nude; Neoplasms; Organometallic Compounds; Oxyquinoline; Prostatic Neoplasms; Pyridines; Radionuclide Imaging; Radiopharmaceuticals; Radiotherapy Dosage; Solubility; Thiones; Treatment Outcome; Tumor Cells, Cultured

The labelling of ex-vivo activated macrophages with doses of 111In-oxine sufficient for gamma camera imaging does not damage cell viability or the functional competence of cells (secretion of tumour necrosis factor-alpha and interleukin-6). The mean labelling efficiency was about 84%. Release of 111In equivalent to 15% occurred over 24 h under cell culture conditions, indicating good stability of the radioactive cell label. 111In-oxine-labelled macrophages are a suitable tool for biokinetic studies of adoptive immunotherapy.

Topics: Cell Survival; Cytotoxicity, Immunologic; Humans; Immunotherapy, Adoptive; In Vitro Techniques; Indium Radioisotopes; Macrophage Activation; Macrophages; Monocytes; Neoplasms; Organometallic Compounds; Oxyquinoline; Radionuclide Imaging

Leukocyte suspensions labeled with In-111 oxine or tropolone were administered intravenously to 150 patients for the detection of suspected foci of bacterial infection by gamma camera imaging. The results were correlated with other imaging modalities, and clinical, laboratory, and surgical findings after a minimum follow-up period of six months. Twenty-five of 29 foci of bacterial infection were demonstrated on the leukocyte-labeled images (sensitivity of detection = 86%). Three of the four missed lesions were chronic active osteomyelitis. The specificity of detection proved difficult to define, varying with different criteria for a false positive diagnosis. In every region of the body, a variety of lesions other than foci of bacterial infection produced positive uptake of the labeled leukocytes. An intense focal uptake was uncommon in lesions other than abscesses and hematomas. It was concluded that imaging with labeled leukocytes is valuable for demonstrating sites of infection in conjunction with other diagnostic methods. Detectable leukocytic infiltration, however, may occur in inflammatory lesions of any cause and in some noninflammatory states as well.

Topics: Abdomen; Abscess; Adult; Aged; Bacterial Infections; False Positive Reactions; Female; Humans; Indium; Joint Diseases; Leukocytes; Male; Middle Aged; Mouth Diseases; Neoplasms; Organometallic Compounds; Osteomyelitis; Oxyquinoline; Pelvis; Radioisotopes; Radionuclide Imaging; Respiratory Tract Infections; Sinusitis; Tropolone

A simultaneous investigation of platelet regeneration time (PRT) based upon malondialdehyde (MDA) recovery after a single oral intake of 500 mg of aspirin and of platelet survival time (PST) after labelling with 51chromium or 111indium oxine was performed in 25 cancerous patients. A pilot study conducted with 9 healthy volunteers demonstrated that the MDA assay was highly reproducible and specific for the platelet cycloxygenase activity. The pattern of MDA recovery after aspirin ingestion was linear in the healthy volunteers and in the patients presenting both a normal and an accelerated platelet turnover. PST were calculated using the four mathematical models recommended by the International Committee for Standardization in Hematology; the best fit was given by the multiple hit model in 22 cases and by the linear regression model in 3 cases. The mean results obtained in the patients investigated with the 51chromium were consistently shorter than those obtained in the patients investigated with the 111indium oxine while the mean PRT were almost identical in the two groups. An excellent correlation between PRT and PST was observed after 111indium oxine labelling and using the weighted mean method for PST determination. These results suggest that the 111indium oxine technique is a better method for platelet labelling and that the results provided by the weighted mean method reflect more closely the in vivo platelet turnover than those provided by the multiple hit model.

Topics: Adult; Aspirin; Blood Platelets; Cell Survival; Chromium Radioisotopes; Female; Humans; Hydroxyquinolines; Indium; Isotope Labeling; Male; Malondialdehyde; Neoplasms; Organometallic Compounds; Oxyquinoline; Radioisotopes; Time Factors

At least one microCi of 111indium oxine (111InOx) could be incorporated into 10(6) human tumor cells without cytotoxicity as determined by colony assay or by trypan blue staining. 111In bound to prekilled cells was removed preferentially by washings, and prelabeled cells killed with diphtheria toxin released radioactivity much more rapidly than did viable cells. The metal chelator calcium disodium edetate did not facilitate 111In removal from either viable or dead cells. High sensitivity can be obtained for in vitro or in vivo cytotoxicity assays using human cells prelabeled with 111InOx.

Topics: Animals; Cell Line; Cell Survival; Deoxyuridine; Diphtheria Toxin; Edetic Acid; Half-Life; Humans; Hydroxyquinolines; Indium; Iodine Radioisotopes; Isotope Labeling; Mice; Mice, Nude; Neoplasms; Organometallic Compounds; Oxyquinoline; Radioisotopes

One hundred twenty-nine 111In-oxine-labeled leukocyte scintiscans have been performed in 117 patients with cancer in order to diagnose localized infectious disease. Of the 115 contributive scans, 40 were in patients with localizing signs, whereas in 75 fever of unknown origin constituted the indication for this examination. The overall specificity of the method was 95.4%, the overall sensitivity 86%, and the global accuracy 91.3%. In 10 cases with localizing signs, the 111In-oxine granulocyte scintigram allowed exclusion of the diagnosis of infection, whereas in 17 instances without localizing signs, a focal infectious process was demonstrated. Heterologous donor leukocytes were used successfully in five instances. With the exception of accumulation of label at the site of an osteolytic metastasis in one case, no uptake was observed in primary or secondary tumors. It is concluded that 111In-oxine-labeled leukocytes constitute a valuable tool in the diagnosis and localization of infection in patients with malignant disease.

Topics: Bacterial Infections; Bone Neoplasms; Diagnosis, Differential; False Negative Reactions; Female; Humans; Hydroxyquinolines; Indium; Leukemia, Lymphoid; Leukocytes; Liver Neoplasms; Lymphoma; Neoplasms; Organometallic Compounds; Oxyquinoline; Radioisotopes; Radionuclide Imaging; Rectal Neoplasms; Uterine Cervical Neoplasms