strontium-radioisotopes and Fibrosarcoma

An unsymmetrically substituted porphyrin, 5-[4-(3-amino)-n-propyloxyphenyl]-10,15,20-tris-(4-carboxymethyleneoxyphenyl)porphyrin, was synthesized and coupled with p-NCS-benzyl-DOTA [p-isothiocyanato-benzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid] for exploring its possible potential in targeted tumor therapy. The porphyrin-DOTA conjugate was radiolabeled with 90Y, obtained from a 90Sr/90Y electrochemical generator, developed in-house. Biodistribution studies performed in Swiss mice bearing fibrosarcoma tumor showed good tumor uptake (∼3.4% injected activity in per g of tumor) within 30 minutes postinjection. The tumor activity decreased with the progress of time, however, tumor to blood and tumor to muscle ratios considerably increased at 4 days postadministration owing to the clearance of the initially accumulated activities from the nontarget organs. The nonaccumulated activity exhibited major clearance through renal pathway.

Topics: Animals; Female; Fibrosarcoma; Heterocyclic Compounds, 1-Ring; Kidney; Mice; Porphyrins; Radioisotopes; Radiopharmaceuticals; Radiotherapy; Spectroscopy, Fourier Transform Infrared; Strontium Radioisotopes; Time Factors; Tissue Distribution; Yttrium Radioisotopes

The natural radiographic appearance of the various bones of the skeleton are described for several strains of laboratory mice. The Harwell substrains of CBA, A and 101 are generally similar and become osteoporotic on ageing. Harwell C57BL have similar, but more delicately chiseled, bones. Harwell C3H mice have bones with stouter cortices and may show osteosclerosis on ageing. CF1 females (donated by Dr M. Finkel) showed osteosclerosis and osteophytic outgrowths when aged. NMRI mice (donated by Dr A. Luz) appeared larger than the pure-strain Harwell mice. In general, mouse bones are simple tubular structures with an ivory cortex and a marrow cavity. Cancellous trabecular bone is scanty, even in vertebrae, flat bones and the metaphyses of long bones. Bone-seeking radionuclides administered to mice lead to skeletal tumours: (a) osteosarcomata, which are commonly radio-opaque to a variable degree owing to calcified tumour bone, but which may be osteolytic, (b) primitive mesenchymal (angio-) sarcomata which are non-osteogenic and osteolytic, (c) fibrosarcomata--which also are osteolytic--and to local or general lymphomata from irradiation of parental cells in bone marrow, but no special radiological features have been found associated with these last-named tumours.

Topics: Aging; Animals; Bone and Bones; Bone Neoplasms; Fibrosarcoma; Hemangiosarcoma; Lymphoma; Mice; Mice, Inbred A; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred Strains; Neoplasms, Radiation-Induced; Osteosarcoma; Plutonium; Radiography; Radium; Species Specificity; Strontium Radioisotopes

Beta-emitting radionuclides are important constituents of isotope inventories in light water reactors and may pose an inhalation hazard to industrial workers or the general population if they are released. To study the biological effects of such potential exposures, a series of life span studies was initiated in which beagle dogs were exposed to aerosols of relatively insoluble fused clay particles containing 90Y, 91Y, 144Ce or 90Sr. Groups of dogs exposed to each radionuclide received graded initial lung burdens of radioactivity. When combined with the varied physical half-lives of the four radionuclides, this resulted in a wide variety of radiation doses and dose patterns to the lung. Deaths (greater than 640 days after exposure) were generally associated with pulmonary neoplasia in dogs that inhaled 91Y, 144Ce or 90Sr. These dogs had cumulative lung doses to death greater than 20 000 rads. Exposure to 144Ce or 90Sr with dose rates that decreased slowly induced pulmonary haemangiosarcomas. Pulmonary irradiation from 91Y, with a rapidly decreasing dose rate, resulted in pulmonary epithelial tumours. No malignant lung tumours have been seen within 1540 days after exposure to 90Y. The animals in the main studies have been observed for 1342 to 2756 days after exposure.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Aerosols; Animals; Carcinoma, Squamous Cell; Cerium Radioisotopes; Dogs; Female; Fibrosarcoma; Hemangiosarcoma; Lung Neoplasms; Male; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Radiation Dosage; Strontium Radioisotopes; Time Factors; Yttrium Radioisotopes

Tumours induced in mice, either CBA normal and chimaerical, or C3H, by (90)Sr or (226)Ra or plutonium have been examined histochemically with (1) diazotate fast red violet LB salt in naphthol AS-MX phosphate buffer at pH 8·6 and 5·2, (2) 1: 9 dimethyl methylene blue (Taylor).It is concluded:(a) The diagnosis of osteosarcoma is facilitated with Taylor's Blue which stains osteoid metachromatically. Cells of osteosarcoma, like normal osteoblasts, contain alkaline phosphatase but this may be lost by mutation either in the original tumour or subsequently on passage of the tumour serially to compatible hosts.(b) Osteosarcomata may contain giant-cells of two forms, bizarre tumour cells and osteoclasts; the latter contain acid phosphatase. Osteosarcomata which retain their osteoid on serial passage have few cells containing acid phosphatases.(c) Primitive mesenchymal cell tumours of angiomatous form may occur, if the bone marrow is irradiated, e.g. by (90)Sr-(90)Y and Pu. These tumours lack osteoid and cells interpretable as osteoblasts or osteoclasts (though they destroy bone).(d) Tumours classifiable as fibrosarcomata occur rarely, and may be truly of fibroblastic origin or be mutated osteosarcomata.(e) Lymphomata also occur when the marrow is irradiated ((90)Sr-(90)Y and Pu). They may be generalized, when their cells may contain alkaline phosphatase or lack it. They may be localized to abdominal viscera, the reticulo-sarcomatous form, in which case the cells lack alkaline phosphatase.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Clinical Enzyme Tests; Color; Coloring Agents; Fibrosarcoma; Hemorrhage; Histocytochemistry; Lymphoma; Mesenchymoma; Mice; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Osteosarcoma; Phosphoric Monoester Hydrolases; Plutonium; Radiation Dosage; Radioisotopes; Radium; Staining and Labeling; Strontium Radioisotopes; Succinate Dehydrogenase; Yttrium Isotopes

Topics: Bone Neoplasms; Chondrosarcoma; Fibrosarcoma; Humans; Lymphoma, Large B-Cell, Diffuse; Osteosarcoma; Radiography; Radionuclide Imaging; Sarcoma; Sarcoma, Ewing; Strontium Isotopes; Strontium Radioisotopes; Technetium

Topics: Animals; Carcinoma, Squamous Cell; Fibrosarcoma; Mice; Neoplasms, Experimental; Phosphorus; Phosphorus Radioisotopes; Sarcoma, Experimental; Skin; Skin Neoplasms; Strontium; Strontium Radioisotopes