Potential of ¹⁰⁹Pd-Labeled Lymphocytes for Selective Lymphatic Ablation

Summary

The biodistribution of lymphocytes labeled with ¹⁰⁹Pd was investigated in Lewis rats to determine if they might be useful for selective lymphoid ablation. ¹⁰⁹Pd-labeled lymphocytes demonstrated significant lymphoid localization. However, there was a fall in the accumulation of radiolabeled lymphocytes in lymphoid tissue when the ¹⁰⁸Pd carrier dose or the ¹⁰⁹Pd radioactive dose incorporated per 10⁸ lymphocytes was increased from 0.12 mg to 0.20 mg and from 21.3 µCi to 54.6 µCi, respectively (P <0.001). ¹⁰⁹Pd-labeled syngeneic and allogeneic lymphocytes demonstrated similar tissue distribution patterns. These results raise the possibility of using ¹⁰⁹Pd-labeled lymphocytes for selective lymphoid ablation, but emphasize the need for using high specific activity ¹⁰⁹Pd and large amounts of lymphocytes for labeling. This will minimize cell damage and allow maximum therapeutic results to be obtained. The use of large numbers of cells might best be accomplished by using donor lymphocytes.

Zusammenfassung

Die Bio verteilung ¹⁰⁹Pd-markierter Lymphozyten wurden in Lewis-Ratten untersucht, um ihre mögliche Verwendung zur selektiven lymphoiden Ablation zu bestimmen. Mit ¹⁰⁹Pd-markierte Lymphozy ten zeigten eine signifikante Anreicherung im Lymphgewebe. Wurde allerdings die ¹⁰⁸Pd-Trägerdosis oder ¹⁰⁹PdRadioaktivitätsdosis, die pro 10⁸ Lymphozyten inkorporiert wurde, von 0,12 mg auf 0,2 mg bzw. von 21,3 µCi auf 54,6 µCi erhöht, so nahm die Anreicherung radioaktiv markierter Lymphozyten im Lymphgewebe ab (p <0.001). ¹⁰⁹Pd-markierte syngenetische und allogenetische Lymphozyten zeigten ähnliche Gewebsverteilungsmuster. Diese Ergebnisse zeigen die Möglichkeit auf, ¹⁰⁹Pd-markierte Lymphozyten zur lymphoiden Ablation anzuwenden, unterstreichen aber andererseits die Notwendigkeit, ¹⁰⁹Pd mit hoher spezifischer Aktivität und große Mengen von Lymphozyten für die Markierung einzusetzen. Durch diese Maßnahmen kann der geringste Zellschaden und der größte therapeutische Effekt erzielt werden. Die Anwendung großer Zellzahlen wird am besten durch die Anwendung von Spenderlymphozyten bewerkstelligt.

• References

• 1 Ackerman G. A., Bellios N. C., Knouff R. A.. et al.: Cytochemical changes in lymph nodes and the spleen of rats after total body X-radiation. Blood 1954; 09: 795-803.
• 2 Billingham R. E., Brent L, Medawar P. B. Quantitative studies on tissue transplantation immunity. II. The origin, strength and duration of activity and adoptively acquired immunity. Proc. Roy. Soc. Lond. (Biol.) 1955; 143: 58-80.
• 3 Chisholm P. M., Danpure H. J., Healey G. et al.: Cell damage resulting from the labeling of rat lymphocytes and Hela 53 cells with ¹¹¹In-oxine J. nucl. Med 1979; 20: 1308-11.
• 4 Fawwaz R, Hemphill W, Winchell H. S. Potential use of ¹⁰⁹Pd-porphyrin complexes for selective lymphatic ablation. J. nucl. Med 1971; 12: 231-6.
• 5 Fawwaz R. A., Kuromoto N, Wang T. S. T. et al.: Effect of Cyclosporin A on migration of ¹¹¹ln lymphocytes. J. nucl. Med 1983; 24: P100.
• 6 Gershim-Cohen J, Hermel M. B. The diagnostic value of the immediate peripheral leukocyte response of the rat to whole body irradiation. Amer. J. Roentgenol 1954; 71: 846-52.
• 7 Gowans J. L. The role of lymphocytes in the destruction of hemografts. Brit. med. Bull 1965; 21: 106-10.
• 8 Hardy M. A., Fawwaz R. A., Oluwole S. et al.: Selective lymphoid irradiation. I. An approach to transplantation. Surgery 1979; 86: 194-202.
• 9 Hume D. W., Wolf J. S. Abrogation of the immune response: Irradiation therapy and lymphocyte depletion. Modification of renal homograft rejection by irradiation. Transplantation 1967; 05: 1174-91.
• 10 Iga C, Fawwaz R. A., Hardy M. A.. et al.: Selective lymphoid ablation and thymectomy in induction of permanent cardiac allograft acceptance in rats. Transplantation. (in press).
• 11 Issekutz T, Chin W, Hay J. B. Measurement of lymphocyte traffic with ¹¹¹Indium. Clin. exp. Immunol 1980; 39: 215-21.
• 12 Oluwole S, Hardy M. A., Fawwaz R. A.. et al.: Selective lymphoid irradiation. II. Comparison with total body irradiation on cardiac allograft survival in rats. Transplantation 1979; 28: 492-5.
• 13 Oluwole S, Satake K, Kuromoto N. et al.: Recirculation of ¹¹¹In-labeled lymphocytes in normal and allografted rats. Transplantation 1981; 31: 51-5.
• 14 Roberts P. J., Hayry P. Effector mechanism in allograft rejection. II. Density, electrophoresis and size fractioning of allograft-infiltrating cells demonstrating serial classes of killer cells. Cell Immunol 1977; 30: 236-53.
• 15 Schroeder S. C., Cawghran M, Jockelson M. Imaging of lymphoid structures with ¹¹¹Indium labeled lymphocytes. Investig. Radiol 1983; 18: 87-93.
• 16 Sparshot M, Sharma H, Kelly J. D., Ford W. L. Factors influencing the fate of ¹¹¹Indium-labeled lymphocytes after transfer to syngeneic rats. J. immunol. Methods 1981; 41: 303-20.
• 17 Thakur M. L., Coleman R. E., Mayhall C. G.. et al.: Preparation and evaluation of ¹¹¹In-labeled leukocytes as an abscess imaging agent in dogs. Radiology 1976; 119: 731-2.
• 18 Wagstaff J, Gibson C, Thatcher W. et al.: A method for following human lymphocyte traffic using ¹¹¹Indium-oxine labeling. Clin. exp. Immunol 1981; 43: 435-42.
• 19 Wang T ST, Oluwole S, Fawwaz R. A.. et al.: Cellular basis of ¹¹¹Inlabeled leukocytes and platelets accumulation in cardiac allografts. J. nucl. Med 1982; 23: 99-7.