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. 1995 Dec;72(6):1541–1546. doi: 10.1038/bjc.1995.544

High-dose gallium-67 therapy in patients with relapsed acute leukaemia: a feasibility study.

A R Jonkhoff 1, M A Plaizier 1, G J Ossenkoppele 1, G J Teule 1, P C Huijgens 1
PMCID: PMC2034096  PMID: 8519674

Abstract

Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105 mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 microCi ml-1, indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi-1. Red marrow dose was estimated to be between 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi-1. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia.

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Selected References

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  1. Ando A., Ando I., Hiraki T., Hisada K. Relation between the location of elements in the periodic table and various organ-uptake rates. Int J Rad Appl Instrum B. 1989;16(1):57–80. doi: 10.1016/0883-2897(89)90216-x. [DOI] [PubMed] [Google Scholar]
  2. Anghileri L. J., Heidbreder M. On the mechanism of accumulation of 67Ga by tumors. Oncology. 1977;34(2):74–77. doi: 10.1159/000225187. [DOI] [PubMed] [Google Scholar]
  3. Chitambar C. R., Seligman P. A. Effects of different transferrin forms on transferrin receptor expression, iron uptake, and cellular proliferation of human leukemic HL60 cells. Mechanisms responsible for the specific cytotoxicity of transferrin-gallium. J Clin Invest. 1986 Dec;78(6):1538–1546. doi: 10.1172/JCI112746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Engelstad B., Luk S. S., Hattner R. S. Altered 67Ga citrate distribution in patients with multiple red blood cell transfusions. AJR Am J Roentgenol. 1982 Oct;139(4):755–759. doi: 10.2214/ajr.139.4.755. [DOI] [PubMed] [Google Scholar]
  5. Hall S. W., Yeung K., Benjamin R. S., Stewart D., Valdivieso M., Bedikian A. Y., Loo T. L. Kinetics of gallium nitrate, a new anticancer agent. Clin Pharmacol Ther. 1979 Jan;25(1):82–87. doi: 10.1002/cpt197925182. [DOI] [PubMed] [Google Scholar]
  6. Hofer K. G., Harris C. R., Smith J. M. Rdiotoxicity of intracellular 67Ga, 125I and 3H. Nuclear versus cytoplasmic radiation effects in murine L1210 leukaemia. Int J Radiat Biol Relat Stud Phys Chem Med. 1975 Sep;28(3):225–241. doi: 10.1080/09553007514550991. [DOI] [PubMed] [Google Scholar]
  7. Huijgens P. C., Jonkhoff A. R., Hoekstra O. S., Ossenkoppele G. J., Teule G. J. Therapeutic potential of intravenous 67-gallium in non-Hodgkin's lymphoma. Eur J Haematol. 1993 Oct;51(4):206–208. doi: 10.1111/j.1600-0609.1993.tb00631.x. [DOI] [PubMed] [Google Scholar]
  8. Jonkhoff A. R., Huijgens P. C., Versteegh R. T., van Dieren E. B., Ossenkoppele G. J., Martens H. J., Teule G. J. Gallium-67 radiotoxicity in human U937 lymphoma cells. Br J Cancer. 1993 Apr;67(4):693–700. doi: 10.1038/bjc.1993.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jonkhoff A. R., Huijgens P. C., Versteegh R. T., van Lingen A., Ossenkoppele G. J., Dräger A. M., Teule G. J. Radiotoxicity of 67-gallium on myeloid leukemic blasts. Leuk Res. 1995 Mar;19(3):169–174. doi: 10.1016/0145-2126(94)00130-3. [DOI] [PubMed] [Google Scholar]
  10. Jonkhoff A. R., von Dieren E. B., Huijgens P. C., Versteegh R. T., Dräger A., vd Loosdrecht A. A., Teule G. J. Biological effectiveness of 67-gallium decay in HL60 cells compared with external low dose rate gamma irradiation: effects on proliferation, G2 arrest, and clonogenic capacity. Int J Radiat Oncol Biol Phys. 1994 Aug 30;30(1):117–124. doi: 10.1016/0360-3016(94)90526-6. [DOI] [PubMed] [Google Scholar]
  11. Kaminski M. S., Zasadny K. R., Francis I. R., Milik A. W., Ross C. W., Moon S. D., Crawford S. M., Burgess J. M., Petry N. A., Butchko G. M. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med. 1993 Aug 12;329(7):459–465. doi: 10.1056/NEJM199308123290703. [DOI] [PubMed] [Google Scholar]
  12. Kelsen D. P., Alcock N., Yeh S., Brown J., Young C. Pharmacokinetics of gallium nitrate in man. Cancer. 1980 Nov 1;46(9):2009–2013. doi: 10.1002/1097-0142(19801101)46:9<2009::aid-cncr2820460919>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  13. Makrigiorgos G., Adelstein S. J., Kassis A. I. Auger electron emitters: insights gained from in vitro experiments. Radiat Environ Biophys. 1990;29(2):75–91. doi: 10.1007/BF01210552. [DOI] [PubMed] [Google Scholar]
  14. Nelson B., Hayes R. L., Edwards C. L., Kniseley R. M., Andrews G. A. Distribution of gallium in human tissues after intravenous administration. J Nucl Med. 1972 Jan;13(1):92–100. [PubMed] [Google Scholar]
  15. Plaizier M. A., Roos J. C., Teule G. J., van Dieren E. B., den Hollander W., Haisma H. J., DeJager R. L., van Lingen A. Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies. Eur J Nucl Med. 1994 Mar;21(3):216–222. doi: 10.1007/BF00188669. [DOI] [PubMed] [Google Scholar]
  16. Press O. W., Eary J. F., Appelbaum F. R., Martin P. J., Badger C. C., Nelp W. B., Glenn S., Butchko G., Fisher D., Porter B. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med. 1993 Oct 21;329(17):1219–1224. doi: 10.1056/NEJM199310213291702. [DOI] [PubMed] [Google Scholar]
  17. Rao D. V., Howell R. W. Time-dose-fractionation in radioimmunotherapy: implications for selecting radionuclides. J Nucl Med. 1993 Oct;34(10):1801–1810. [PubMed] [Google Scholar]
  18. Schwartz M. A., Lovett D. R., Redner A., Finn R. D., Graham M. C., Divgi C. R., Dantis L., Gee T. S., Andreeff M., Old L. J. Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias. J Clin Oncol. 1993 Feb;11(2):294–303. doi: 10.1200/JCO.1993.11.2.294. [DOI] [PubMed] [Google Scholar]
  19. Sephton R., Martin J. J. Modification of distribution of gallium 67 in man by administration of iron. Br J Radiol. 1980 Jun;53(630):572–575. doi: 10.1259/0007-1285-53-630-572. [DOI] [PubMed] [Google Scholar]
  20. Tanswell P., Koup J. TopFit: a PC-based pharmacokinetic/pharmacodynamic data analysis program. Int J Clin Pharmacol Ther Toxicol. 1993 Oct;31(10):514–520. [PubMed] [Google Scholar]
  21. Vallabhajosula S. R., Harwig J. F., Siemsen J. K., Wolf W. Radiogallium localization in tumors: blood binding and transport and the role of transferrin. J Nucl Med. 1980 Jul;21(7):650–656. [PubMed] [Google Scholar]
  22. van Leeuwen-Stok A. E., Dräger A. M., Schuurhuis G. J., Platier A. W., Teule G. J., Huijgens P. C. Gallium 67 in the human lymphoid cell line U-715: uptake, cytotoxicity and intracellular localization. Int J Radiat Biol. 1993 Dec;64(6):749–759. doi: 10.1080/09553009314552001. [DOI] [PubMed] [Google Scholar]

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