phosphorus-radioisotopes and Osteosarcoma

Topics: Bone Neoplasms; Energy Metabolism; Humans; Magnetic Resonance Spectroscopy; Osteosarcoma; Phosphorus Radioisotopes; Sensitivity and Specificity

In vivo studies have demonstrated that pentavalent technetium-99m dimercaptosuccinic acid [(99m)Tc-(V)-DMSA] may be a useful tumour imaging agent. Several studies have suggested that (99m)Tc-(V)-DMSA uptake may be related to the structural similarity between the (99m)Tc-(V)-DMSA core and the PO(4)(3-) anion. As phosphate ions enter cells via NaPi cotransporters, we investigated whether (99m)Tc-(V)-DMSA uptake is mediated by NaPi cotransporters. (99m)Tc-(V)-DMSA and phosphate uptake kinetics were compared in three cancer cell lines (MCF-7, G152 and MG-63) under several conditions (with and without sodium and NaPi cotransporter inhibitor and at different pH). Determination of molecular NaPi cotransporter mRNA expression was performed by reverse-transcriptase polymerase chain reaction (Rt-PCR) assay. Results obtained in the presence of NaPi inhibitor, in sodium-free medium and at alkaline pH showed that (99m)Tc-(V)-DMSA accumulation is linked to NaPi cotransporter functionality. MCF-7 and G152 exhibited the same tracer uptake, whereas MG-63 showed the highest phosphate accumulation and the lowest (99m)Tc-(V)-DMSA uptake. These results were in accordance with mRNA NaPi expression, i.e. all cell lines expressed NaPi type III but MG-63 also co-expressed NaPi type I. The total level of NaPi cotransporter was highly correlated with phosphate accumulation, while the level of type III was related to (99m)Tc-(V)-DMSA uptake. We have demonstrated that (99m)Tc-(V)-DMSA uptake is specifically mediated by NaPi type III in cancer cells.

Topics: Biomarkers, Tumor; Breast Neoplasms; Cell Line, Tumor; Glioblastoma; Humans; Hydrogen-Ion Concentration; Kinetics; Metabolic Clearance Rate; Neoplasms; Osteosarcoma; Phosphates; Phosphorus Radioisotopes; Potassium Compounds; Radionuclide Imaging; Radiopharmaceuticals; Sodium; Sodium-Phosphate Cotransporter Proteins; Sodium-Phosphate Cotransporter Proteins, Type I; Symporters; Technetium Tc 99m Dimercaptosuccinic Acid

Two rat osteosarcoma cell lines, YROS-1 and YROS-2, were established from two experimental osteosarcomas and induced by internal irradiation with radioactive phosphorus. Both cell lines formed a monolayer cell sheet in vitro with focal piling. The YROS-1 cells were refractile and spindle or polygonal in shape, whereas the YROS-2 cells were flat, spread and polygonal in shape. Ultrastructurally, the YROS-1 cells had well-developed rough-surfaced endoplasmic reticulum with focal pericellular deposition of calcified matrix, whereas YROS-2 had abundant polysomes and intracytoplasmic filaments. Both cell lines grew stably with population doubling times of 23 and 39 h, respectively. Flow cytometry revealed that YROS-1 was rich in proliferating cells compared to YROS-2, with a higher colony-forming efficiency. YROS-1 showed high alkaline phosphatase activity, while YROS-2 possessed low activity. When subcutaneously transplanted into lumbodorsal area of athymic nude mice, only YROS-1 formed tumors with frequent lung metastasis.

Topics: Animals; Cell Division; Female; Injections, Intraperitoneal; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Osteosarcoma; Phosphorus Radioisotopes; Rats; Rats, Wistar; Tumor Cells, Cultured

In search of a predictable experimental model for the study of therapeutic modalities for osteosarcoma, a group of rats had injections of phosphorus-32 (P-32) colloid subperiostally and were followed for the occurrence of malignant bone tumors until death or for 18 months. Of 50 rats, 26 died of unrelated causes and only 24 were included in the study. Two cases of osteosarcomas, one occurring in month 16 and the other at month 18 were induced; one case demonstrated multiple lung metastases. Clear evidence of the sarcoma inducing effect of P-32 has been obtained in this study. However, a high yield experimental osteosarcoma model was not produced.

Topics: Animals; Bone Neoplasms; Male; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphorus Radioisotopes; Rats; Rats, Wistar; Time Factors

Insulin-like growth factor I (IGF-I) stimulates multiplication of the human osteosarcoma cell line, MG-63. by acting through the IGF-I receptor. We have characterized IGF-I stimulated phosphorylation of the IGF-I receptor in this cell line. Serum starved MG-63 cells were metabolically labeled with [32P]orthophosphoric acid and the cells were treated with IGF-I. Phosphotyrosine containing proteins were immunoprecipitated from the cell lysates with antiphosphotyrosine-Agarose and eluted with phenyl phosphate. Further immunoprecipitation with IGF-I receptor monoclonal antibodies (alpha IR-3, 18E9) and analysis by sodium dodecylsulfate polyacrylamide gel electrophoresis and autoradiography demonstrated IGF-I dependent autophosphorylation of the IGF-I receptor. Phosphoamino acid analysis of the IGF-I receptor beta subunit and the observation that antiphosphotyrosine-Agarose did not immunoprecipitate [35S]methionine-labeled receptor from unstimulated cells, demonstrated that in the absence of IGF-I, the receptor was not phosphorylated on tyrosine residues. Western blotting of cell lysates with a monoclonal phosphotyrosine antibody did not identify the IGF-I receptor or pp185 but demonstrated IGF-I dependent phosphorylation on tyrosine residues in three other proteins, p110, p70 and p40.

Topics: Blotting, Western; Cell Line; Electrophoresis, Polyacrylamide Gel; Humans; Insulin-Like Growth Factor I; Kinetics; Molecular Weight; Osteosarcoma; Phosphates; Phosphoproteins; Phosphorus Radioisotopes; Phosphorylation; Phosphotyrosine; Receptor, IGF Type 1; Tumor Cells, Cultured; Tyrosine

The purpose of this study was to determine the response of bone cells to physical stress. Intermittent compressive force (ICF) was applied to 13 kPa to subconfluent ROS 17/2.8 cells at 18 cycles/min. After 48 h of this application, the cells were labelled with [35S]-methionine or [32PO4]. Application of ICF over this time did not alter the synthesis of type I collagen, fibronectin or bone SPARC (osteonectin) compared to that of control cells. However, the activity of alkaline phosphatase was increased 1.5-fold, and the synthesis of a 32PO4-labelled, 75-kDa phosphoprotein, recognized as osteopontin by immunoprecipitation with specific antibodies, was increased 1.4-fold. Also, an increase in osteopontin mRNA starting within 12h of ICF application was observed. The selective increase in osteopontin expression associated with ICF may be important in the remodelling of bone tissues during growth and development and in response to functional forces.

Topics: Alkaline Phosphatase; Animals; Bone Matrix; Cell Adhesion; Cell Line; Collagen; Fibronectins; Gelatinases; Gene Expression; Osteonectin; Osteopontin; Osteosarcoma; Pepsin A; Phosphoproteins; Phosphorus Radioisotopes; Precipitin Tests; Rats; RNA, Messenger; Sialoglycoproteins; Stress, Mechanical; Sulfur Radioisotopes

Topics: 3-O-Methylglucose; Biological Transport; Humans; Kinetics; Methylglucosides; Osteoblasts; Osteosarcoma; Phosphates; Phosphorus Radioisotopes; Tritium; Tumor Cells, Cultured

Radioactive phosphorus (P-32) was administered intraperitoneally to Wistar female rats at 2-week intervals. P-32 was administered at a total dose of 3 mCi (a single dose of 200 microCi, 15 times) to Group 1, 2.4 mCi (1 microCi/g body weight, 15 times) to Group 2, and 1.4 mCi (1 microCi/g, 10 times) to Group 3. Osteosarcoma was induced in 29 out of 80 rats (36%) in Group 1, 28 out of 40 (70%) in Group 2, and 31 out of 40 (78%) in Group 3. Bone tumor was predominant in the trunk (spine, ilium etc.) in Group 1 (86%), and in the extremities (femur, tibia etc.) in Group 2 (64%) and Group 3 (71%). Histological findings revealed neoplastic osteoid formation in all lesions. Osteoblastic type developed more in Group 1 than in Group 3, and fibroblastic type developed more in Group 3 than in Group 1. The rate of lung metastasis was significantly higher in Group 3 (94%) than in Group 1 (21%, p less than 0.01) or Group 2 (72%, p less than 0.05). This experimental method, especially that used for Group 3, appears to be useful for studying the basis of human osteosarcoma.

Topics: Animals; Body Weight; Female; Lung Neoplasms; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; Sarcoma, Experimental

Chromic colloidal phosphate labeled with 32P, which has been proposed for the treatment of several articular diseases, was injected intra-articularly in the knee joint of adult Wistar rats. After a 270 days minimum latent period, tumors began to appear in the injected zone, to a 70% frequency. Ten lung metastases were detected. In five cases, squamous cell carcinomas were induced in the injected area. The relevance of a sound evaluation of the risk involved in treatments with radioactive isotopes, is discussed.

Topics: Animals; Carcinoma, Squamous Cell; Hindlimb; Injections, Intra-Articular; Joint Diseases; Joints; Lung Neoplasms; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains

1 An attempt was made to produce a model of osteogenic sarcoma using 32P transplacentally. 2 Fetal tissues appeared to be resistant to irradiation as no tumour was induced at an increased frequency in treated animals. 3 Tumours that normally occur in our strain (Sprague-Dawley rats) showed a clear tendancy to occur earlier in post-natal life in treated animals compared with controls.

Topics: Animals; Bone Neoplasms; Dose-Response Relationship, Radiation; Female; Fertility; Fetus; Male; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphorus Radioisotopes; Pregnancy; Rats; Rats, Inbred Strains; Sarcoma, Experimental

Topics: Animals; Cobalt Radioisotopes; Disease Models, Animal; Female; Injections, Intraperitoneal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Neoplasm Metastasis; Neoplasm Transplantation; Osteosarcoma; Ovarian Neoplasms; Peritoneal Neoplasms; Phosphorus Radioisotopes; Radioisotope Teletherapy; Sarcoma, Experimental

Topics: Animals; Bone Neoplasms; Cats; Neoplasm Metastasis; Osteosarcoma; Phosphorus Radioisotopes; Rats; Technetium

Topics: Adenylyl Cyclases; Animals; Calcitonin; Cell Membrane; Enzyme Activation; Neoplasm Transplantation; Neoplasms, Experimental; Osteosarcoma; Parathyroid Hormone; Phosphorus Radioisotopes; Prostaglandins; Rats; Sarcoma, Experimental

Topics: Animals; Bone Matrix; Culture Techniques; Femoral Neoplasms; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphorus Radioisotopes; Rats; Sarcoma, Experimental; Tibia; Transplantation, Homologous

Topics: Adolescent; Adult; Bone Neoplasms; Child; Electromagnetic Phenomena; Extremities; Humans; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Osteomyelitis; Osteosarcoma; Phosphorus Radioisotopes

Topics: Animals; Bone Neoplasms; Mice; Neoplasms; Neoplasms, Experimental; Osteosarcoma; Phosphorus; Phosphorus Radioisotopes; Sarcoma

Topics: Bone Neoplasms; Neoplasms; Osteosarcoma; Phosphorus; Phosphorus Radioisotopes; Propiophenones; Radioisotopes