Studies on the Relationship between ⁶⁷Ga-Citrate Accumulation and Calcium Metabolism in Tumor Cells

L’incorporation in vivo du citrate de gallium (⁶⁷Ga) et du chlorure de calcium (⁴⁵Ca) dans les cellules de la tumeur ascitique d’Ehrlich a été étudiée par la technique des “ghost cells”. Les résultats indiquent qu’à peu près 50% du ⁶⁷Ga intracellulaire est incorporé par le matérial cellulaire résiduel qui ist formé principalement par des phospholipides, protéines et acides nucléiques. La relation existant entre les deux incorporations (du ⁶⁷Ga et du ⁴⁵Ca) est discutée.

Summary

The in vivo uptake of ⁶⁷Ga-citrate and ⁴⁵Ca-chloride by Ehrlich ascites tumor cells has been studied by the "ghost cells" technique. The results indicate that approximately 50% of the intracellular ⁶⁷Ga is incorporated into the cellular residual material formed mainly by phospholipids, proteins and nucleic acids. The relationship between both ⁶⁷Ga and ⁴⁵Ca incorporations is discussed.

Die in vivo “uptake” von ⁶⁷Ga-Zitrat und ⁴⁵Ca-Chlorid in Ehrlich-Aszites- Tumorzellen wurde anhand der “ghost cells”-Technik untersucht. Die Ergebnisse lassen erkennen, daß annähernd 50% des intrazellulären ⁶⁷Ga im zellulären Restmaterial, das hauptsächlich aus Phospholipiden, Proteinen und Nukleinsäuren besteht, gespeichert werden. Die Beziehungen zwischen ⁶⁷Ga- und ⁴⁵Ca- Speicherung werden diskutiert.

^* This work has been partially supported by the Ministerium für Wissenschaft und Forschung des Landes Nordrhein-Westfalen.

• References

• 1 Edwards C. L, Hayes R. L. Tumor scanning with ⁶⁷Ga-citrate. J. Nucl. Med 1969; 10: 103.
• 2 Edwards C. L, Hayes R. L, Nelson B. M. Clinical investigation of ⁶⁷Ga for tumor scanning. J. Nucl. Med 1970; 11: 316.
• 3 Langhammer H, Glaubill G, Grebe S. F. et al ⁸⁷Ga for tumor scanning. J. Nucl. Med 1972; 13: 25.
• 4 Higasi T, Nakayama Y. et al Clinical evaluation of ⁶⁷Ga-citrate scanning. J. Nucl. Med 1972; 13: 196.
• 5 Higasi T, Ikemoto S. et al Diagnosis of malignant tumors with ⁶⁷Ga-citratc (1st. report). Jap. J. Nucl. Med 1969; 6: 217.
• 6 Higasi T, Hisada T. et al Diagnosis of malignant tumors with ⁶⁷Ga-citrate (2nd. report). Radioisotopes 1970; 19: 17.
• 7 Bruemer N. C, Thomas L. E. Cellular lipoproteins — II. A "ghost cell" preparation. Exptl. Cell Res 1957; 13: 103.
• 8 Thomas L. E, Levin E. Cellular lipoproteins — IV. The insoluble lipoproteins of various tissues. Exptl. Cell Res 1962; 28: 365.
• 9 Holczinger L, Bálint Z. Chemical composition and electron microscopy of residual lipoproteins of sarcoma 180 and NK-lymphoma ascites tumor cells. Neoplasma 1972; 19: 95.
• 10 Shah D. O, Schulman J. H. Binding of metal ions to monolayers of lecithins, plasmogen, cardiolipin, and diacetylphosphate. J. Lipid Res 1965; 6: 341.
• 11 Rojas E, Tobias J. M. Membrane model: Association of inorganic cations with phospholipids monolayers. Biochim. Biophys. Acta 1965; 94: 394.
• 12 Joos R. W, Carr C. W. The binding of calcium to phospholipidprotein complexes. Proc. Soc. Exptl. Biol. Med 1969; 132: 865.
• 13 Wasserman R. H, Corradino R. A, Taylor A. N. Vitamin D-dependent calcium-binding protein. J. biol. Chem 1968; 243: 3978.
• 14 Pedersen K. O. Binding of calcium to serum albumin. Scand. J. clin. Lab. Invest 1971; 28: 459.
• 15 Anghileri L. J. Studies on the accumulation mechanisms of radioisotopes used in tumor diagnostic. Strahlentherapie 1971; 142: 456.
• 16 Anghileri L. J. Studies on the accumulation mechanisms of ⁶⁷Ga in tumors: role of calcium metabolism. Strahlentherapie 1972; 144: 29.
• 17 Schmidt G, Thannhauser S. J. A method for the determination of desoxyribonucleic acid, ribonucleic acid and phosphoproteins in animal tissues. J. biol. Chem 1945; 161: 88.
• 18 Banerjee D. K, Budke C. C, Miller F. D. Spectrophotometric determination of traces of calcium in sodium — Visible and ultraviolet methods using sodium naphthalhydroxamate. Anal. Chem 1961; 33: 418.
• 19 Fiske C. H, Subbarow Y. The colorimetric determination of phosphorus. J. biol. Chem 1925; 66: 375.
• 20 Anghileri L. J, Miller E. S. Calcium metabolism in tumors: Its relationship with chromium complex accumulation. I. Uptake of calcium and phosphorus by experimental tumors. Oncology 1971; 25: 119.
• 21 Gornal A. G, Bardavill C. J, David M. M. Determination of serum proteins by means of the biuret reaction. J. biol. Chem 1949; 177: 741.
• 22 Dickens F. The citric acid content of animal tissues, with reference to its occurrence in bone and tumour. Biodiem. J 1941; 35: 1011.
• 23 Haven F. L, Randall C, Bloor W. R. The citric acid content of tumor tissue and of tumor-bearing rats. Cancer Res 1949; 9: 90.
• 24 Cavalieri L. F. Studies on the structure of nucleic acids. V. On the mechanism of metal and enzyme interactions. J. Amer. diem. Soc 1952; 74: 1242.
• 25 Wiberg J. S, Neuman W. F. The binding of bivalent metals by deoxyribonucleic and ribonucleic acids. Arch. Biodiem. Biophys 1957; 72: 66.
• 26 Wang T. Y. Metabolic activities of nuclear proteins and nucleic acids. Biochim. Biophys. Acta 1963; 68: 52.
• 27 Anghileri L. J. Role of the tumor phospholipids in the accumulation of ⁶⁷Ga-citrate. J. Nucl. Biol. Med 1972; 16: 21.
• 28 Levinson C, Blumenson L. E. Calcium transport and distribution in Ehrlich ascites tumor cells. J. Cell Physiol 1970; 75: 231.
• 29 Nash H. A, Tobias J. M. Phospholipid membrane model: Importance of phosphatidyl serine and its cation exchanger nature. Proc. Natl. Acad. Sei. (Wash.) 1964; 51: 476.
• 30 Anghileri L. J, Miller E. S. et al Calcium metabolism in tumors: Its relationship with chromium complex accumulation. II. Calcium, magnesium and phosphorus in human and animal tumors. Oncology 1971; 25: 193.