Iron-Binding Proteins and 67Ga Accumulation by Tumor Cells
L. J. Anghileri
1
From the Nuclear Medicine Service and Biophysics Laboratory, Faculty of Medicine, University of Nancy, France
,
P. Thouvenot
1
From the Nuclear Medicine Service and Biophysics Laboratory, Faculty of Medicine, University of Nancy, France
,
Marie-Christine Crone-Escanye
1
From the Nuclear Medicine Service and Biophysics Laboratory, Faculty of Medicine, University of Nancy, France
,
F. Brunotte
1
From the Nuclear Medicine Service and Biophysics Laboratory, Faculty of Medicine, University of Nancy, France
,
J. Robert
1
From the Nuclear Medicine Service and Biophysics Laboratory, Faculty of Medicine, University of Nancy, France
› Author AffiliationsThe authors thank Professor Dr. Klaus Goerttler, Institut für Experimentelle Pathologie, Deutsches Krebsforschungszentrum, Heidelberg, FRG, for the tumors used in this work.
Tumor cells incubated with 67Ga-citrate plus lactoferrin showed a lactoferrin concentration-dependent increase of 67Ga uptake while for transferrin the effect was an inhibition. A correlation was observed between the binding of 131l-labelled lactoferrin or 131l-labelled transferrin and the uptake of 67Ga by the cells. Saturation with iron did not change significantly the effects of the ironbinding proteins. Preincubation with lactoferrin, transferrin or ferric citrate increased 67Ga uptake. The formation of a ternary complex in which 67Ga mimics iron is discussed.
Zusammenfassung
Tumorzellen, die mit 67Ga-Zitrat und Laktoferrin inkubiert wurden, zeigten eine Zunahme der 67Ga-Anreicherung in Abhängigkeit von der Laktoferrin-Konzentration, während mit Transferrin ein inhibitorischer Effekt eintrat. Eine Korrelation wurde zwischen der Bindung von 131I-markiertem Laktoferrin oder 131I-markiertem Transferrin mit der Anreicherung von 67Ga durch die Zellen beobachtet. Die Sättigung mit Eisen veränderte die Wirkungen der eisenbindenden Proteine nicht signifikant. Die vorherige Inkubation mit Laktoferrin, Transferrin oder Eisenzitrat erhöhte die 67Ga-Anreicherung. Die Bildung eines ternären Komplexes, in dem 67Ga Eisen simuliert, wird diskutiert.
REFERENCES
1
Anghileri L J.
Radiotracer localization in inflammatory lesions. In:
Anghileri L J.
ed. General processes of radiotracer localization, Vol. 1. Boca Raton: CRC Press; 1982: 61-3.
2
Anghileri L J,
Crone-Escanye M C,
Thouvenot P.
et al. Mechanisms of gallium accumulation by tumors: role of cell membrane permeability. J Nucl Med 1988; 29: 663-8.
4
Bates G W,
Wernicke J.
The kinetics and mechanism of iron (III) exchange between chelates and transferrin. IV. The reaction of transferrin with iron (III) nitriloacetate. J Biol Chem 1971; 246: 3679-85.
6
Greenwood F G,
Hunter W M,
Glover J S.
The preparation of 131I-labelled human growth hormone of high specific radioactivity. Biochem J 1963; 89: 114-23.
7
Hansen N E,
Karle H,
Andersen V.
et al. Neutrophilic granulocytes in acute bacterial infection. Sequential studies on lysozyme, myeloperoxidase and lactoferrin. Clin Exp Immunol 1976; 26: 463-71.
11
Larson S M,
Rasey J S,
Allen D R.
et al. A transferrin-mediated uptake of gallium-67 by EMT-6 sarcoma. I. Studies in tissue culture. J Nucl Med 1979; 20: 837-42.
12
Larson S M,
Rasey J S,
Allen D R.
et al. A transferrin-mediated uptake of gallium-67 by EMT-6 sarcoma. II. Studies in vivo (BALB/c) mice. J Nucl Med 1979; 20: 843-6.
20
Terner U K,
Noujain A A,
Lentle B C.
et al. The effects of differing gallium-transferrinanion complexes on the tumor uptake of 67Ga. Int J Nucl Med Biol 1981; 08: 357-62.
21
Wong H,
Terner U K,
English D.
et al. The role of transferrin in the in vivo uptake of gallium-67 in a canine tumor. Int J Nucl Med Biol 1980; 07: 9-12.
