Tatsunosuke Hiraki

Biodistributions of 201Tl in tumor bearing animals and inflammatory lesion induced animals

The accumulation of 201Tl in tumor and inflammatory tissues were small. However, this nuclide showed a high concentration in viable tumor tissue, less in connective tissue (containing inflammatory tissues), and was not seen in necrotic tumor tissue regardless of the time after administration of 201Tl(I)-chloride. In inflammatory lesions, 201Tl accumulated in subcutaneous tissue infiltrated with neutrophils and macrophages, and quite large amounts of this nuclide were accumulated in subcutaneous tissue and sites where neutrophils were croeded. Most 201Tl existed in a free form in the fluid of tumor and inflammatory tissues regardless of the time after administration. A small amount of this nuclide was localized in the nuclear, mitochondrial and microsomal fractions in these tissues, and the nuclide was bound to protein in these fractions. The distribution of 201Tl(III)-chloride in tumor bearing animals was essentially the same as that of 201Tl(I)-chloride.

Relation between the location of elements in the periodic table and various organ-uptake rates

Fifty four elements and 65 radioactive compounds were examined to determine the organ uptake rates for rats 3, 24 and 48 h after i.v. injection of these compounds. They were prepared as carrier free nuclides, or containing a small amount of stable nuclide. Generally speaking, behaviors of K, Rb, Cs and Tl in all the organs were very similar to one another, but they differed from that of Na. Bivalent hard acids were avidly taken up into bone; therefore, uptake rates in soft tissues were very small. Hard acids of tri-, quadri- and pentavalence which were taken up into the soft tissue organs decreased more slowly from these organs than other ions. Soft acids such as Hg2+ were bound very firmly to the component in the kidney. Anions (with few exceptions), GeCl4 and SbCl3 were rapidly excreted in urine, so that the uptake rates in organs were low.

Mechanism of tumor and liver concentration of 67Ga: 67Ga binding substances in tumor tissues and liver

Tumor-bearing animals were administered with 67Ga citrate and tumor homogenates, from which nuclear fraction was removed, and mitochondrial fraction of the host livers were digested with protease (pronase P). After digestion, the supernatants of the reaction mixtures were applied to a Sephadex G-100 column. Resultant eluates were analyzed for radioactivity, protein, uronic acid and sialic acids. Three peaks of radioactivity were obtained by gel filtration. The first peak eluted in the void volume contained a species whose molecular weight exceeded 40,000. The second peak consisted of substances with molecular weights of 9400-40,000. Radioactivity in the third peak was from liberated gallium-67. 67Ga in the second peak was bound to acid mucopolysaccharide and/or the sulfated carbohydrate chain of sulfated glycoprotein. It was thought that 67Ga in the first peak might be bound to some acid mucopolysaccharides. Considering the results of cellulose acetate electrophoresis, 67Ga in the second peak seemed to be bound to acid mucopolysaccharide which contained no uronic acids, and/or to the sulfated carbohydrate chain of sulfated glycoprotein. It was concluded that 67Ga was bound to the acid mucopolysaccharides and/or the sulfated carbohydrate chain of sulfated glycoprotein in tumor tissues and liver lysosomes.

Affinity of 167Tm-citrate for tumor and liver tissue

AbstractStrong affinity of 167Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with 167Tm-citrate because of its strong tumor affinity and because of the suitable physical charateristics of 167Tm.A large amount of 167Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. 167Tm was not seen in necrotic tumor tissue.It was concluded that lysosomes did not play a major role in the tumor concentration of 167Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumd that lysosomes played a considerably important role in the tumor concentration of 167Tm, hepatoma AH109A possessing some residual features of the liver. 167Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which 167Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate).

Mechanism of tumor and liver concentration of 111In and 169Yb: 111In and 169Yb binding substances in tumor tissues and liver

Tumor-bearing animals were injected with 111In- and 169Yb-citrate. Tumor homogenates, from which the nuclear fraction was removed, and the mitochondrial fractions of the host livers were digested with pronase P. After digestion, the supernatants of the reaction mixtures were applied to Sephadex G-100 columns. The resultant eluates were analyzed for radioactivity, protein, uronic acid, and sialic acids. Three peaks of radioactivity were obtained by gel filtration. The first peak, eluted in the void volume, contained a species whose molecular weight exceeded 40000. The second peak consisted of substances with molecular weights of 9400–40000. Radioactivity in the third peak was liberated 111In and 169Yb. These two nuclides in the second peak were bound to acid mucopolysaccharide and/or the sulfated carbohydrate chain of sulfated glycoprotein. It was thought that the nuclides in the first peak might be bound to some acid mucopolysaccharides.The second peak nuclides seemed to be bound to acid mucopolysaccharide that contained no uronic acids, and/or to the sulfated carbohydrate chain of sulfated glycoprotein. It was concluded that they were bound to the acid mucopolysaccharides and/or the sulfated carbohydrate chain of sulfated glycoprotein in tumor tissues and liver lysosomes.

Mechanism of gallium 67 accumulation in inflammatory tissue

The present study was undertaken to elucidate the accumulation mechanism of gallium 67 in inflammatory tissue.67Ga accumulation in inflammatory tissue was observed by macro- and microautoradiogram. Permeability indices were calculated for serum albumin from blood vessels into inflammatory and normal tissue. Neutrophils and macrophages did not play a major role in67Ga accumulation in the inflammatory tissue because67Ga could hardly be detected in the sites in which neutrophils were crowded; the accumulation was concentrated in the intercellular space around these cells in the tissue. Permeability indices for inflammatory tissue were much greater than those for normal tissues. It is thought from the present study and previously reported results that67Ga, together with plasma from permeable blood vessels, readily penetrates the inflammatory tissue and stays there by binding to the acid mucopolysaccharide present in the tissue.

Biodistributions of radioactive alkaline metals in tumor bearing animals: comparison with 201Tl

The retention values for 42K, 86Rb and 134Cs in the tissues and blood were quite similar to those for 201Tl, but were very different from those for 22Na. In an experiment for subcellular fractionation of tumors, most of these nuclides were localized in the supernatant fraction, with small amounts in other fractions. The concentration ratios for these nuclides in each fraction were approximately constant regardless of the time after administration. Radioactive alkaline metals in the supernatant fraction of the tumor homogenate existed mostly as free ions and were bound to protein in other fractions of tumor tissue. These results were essentially the same as those for 201Tl. Ouabain suppression studies indicated that 201Tl is taken up into the tumor cells partly through Na+, K+-ATPase of their membranes. Ionic radii of alkaline metals and thallium were related to their blood and tumor retention values. This relationship suggested that monovalent cations whose ionic radii exceed 0.133 nm, and which exist as free ions in the tissue fluids, behave like the potassium ion. Potassium and K analogs (Tl, Rb, Cs) are avidly taken up into viable tumor cells whose Na+, K+-ATPase activity is elevated. Therefore, suitable radionuclides of K and K analogs can be excellent agents for visualization of viable tumor tissues.

Subcellular distribution of gallium-67 in tumor and liver

Abstract Subcellular distribution of 67 Ga was quantitatively determined to evaluate the role of the lysosome in accumulation of 67 Ga in malignant tumor tissue and the liver using three different tumor models and the host liver. In Yoshida sarcoma and Ehrlich tumor, most of the radioactivity of 67 Ga was localized in the supernatant fraction, and only a small amount of radioactivity was localized in the mitochondrial fraction, which contains lysosomes. In the liver, however, most of the radioactivity was concentrated in the mitochondrial fraction. The radioactivity of this fraction increased with time after the administration of 67 Ga and reached approximately 50% of total radioactivity within 24 h. In the case of hepatoma AH 109A, radioactivity of the mitochondrial fraction increased with time after administration, and about 30%, of total radioactivity was concentrated in this fraction after 24 h. It is concluded that lysosome does not play a major role in the tumor concentration of 67 Ga, although it may play an important role in the liver concentration of 67 Ga. In the case of hepatoma AH109A, it is presumed that lysosome plays a considerably important role in the tumor concentration of 67 Ga, hepatoma AH 109A possessing some residual features of the liver.

Subcellular distribution of 111In and 169Yb in tumor and liver

Subcellular distribution of 111In and 169Yb was quantitatively determined to evaluate the role of the lysosome in accumulation of these nuclides in malignant tumor tissue and in the liver using three different tumor models and the host liver. In Yoshida sarcoma and Ehrlich tumor, most of the radioactivity of these nuclides was localized in the supernatant fraction, and only a small amount of radioactivity was localized in the mitochondrial fraction, which contains lysosomes. In the liver, most of the radioactivity was concentrated in the mitochondrial fraction. The radioactivity of this fraction increased with time after the administration of these nuclides and reached approximately 50% of the total radioactivity within 24 h. In the case of hepatoma AH109A, radioactivity of the mitochondrial fraction increased with time after administration, and about 30% of the total radioactivity was concentrated in this fraction after 24 h. It is concluded that the lysosome does not play a major role in the tumor concentration of these nuclides, although it may play an important role in their liver concentration. In the case of hepatoma AH109A, it is presumed that lysosome plays a considerably important role in the tumor concentration of these nuclides, hepatoma AH109A possessing some residual features of the liver.

Tumor and liver uptake models of 67Ga-citrate

AbstractAfter administration 67Ga concentrates with time in lysosomes from the cytoplasm of liver cells. The lysosomal role in the accumulation of 67Ga in the liver cell is weakened upon transformation of the liver cell into a malignant tumor cell. In malignant tumors (except for hepatoma) the lysosome does not play a major role in the tumor concentration of 67Ga. 67Ga is bound to acid mucopolysaccharides (keratan polysulfate, etc.) in both tumor and liver. In liver cells, large amounts of 67Ga are transported into lysosomes with these acid mucopolysaccharides, and in hepatoma cells, quite large amounts of 67Ga are transported into lysosomes with these acid mucopolysaccharides. In malignant tumor cells (except for hepatoma) the effect is much smaller, the acid mucopolysaccharides transporting very little 67Ga into lysosome.The 67Ga is concentrated in viable tumor tissue within malignant tissue but hardly at all in necrotic tumor tissue, and concentrates avidly in inflammatory infiltration around tumor cells. Plenty of 67Ga is found in liver but very little in connective tissue associated with the liver.