Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Appelbaum, F.R. et al.

Specific marrow ablation before marrow transplantation using an aminophosphonic acid conjugate 166Ho-EDTMP.

166Holmium ethylenediaminetetramethylene phosphonic acid (166Ho-EDTMP) is a short-lived beta-emitting radionuclide complexed to an aminophosphonate ligand that we have investigated in a canine model as a potential agent for specific marrow ablation before marrow transplantation. After intravenous injections, 166Ho-EDTMP distributed principally to bone and after 24 hours the concentrations of 166Ho-EDTMP in bone were more than 200-fold higher than in any other organ. Increasing dosages of 166Ho-EDTMP led to increasingly prolonged and severe myelosuppression, but myeloablation was not achieved. Histologic examination of recovering animals suggested that the spleen may have acted as a reservoir for circulatory hematopoietic precursors. Four splenectomized animals administered 20 to 30 mCi/kg 166Ho-EDTMP without marrow transplantation died with marrow aplasia, while four splenectomized animals administered similar dosages of 166Ho-EDTMP followed by autologous transplantation recovered. The dose-limiting toxicity of 166Ho-EDTMP appeared to be marrow stromal damage resulting in myelofibrosis, which was reversible. These results suggest that 166Ho-EDTMP can be used to specifically ablate marrow function before marrow transplantation.[1]

References

Specific marrow ablation before marrow transplantation using an aminophosphonic acid conjugate 166Ho-EDTMP. Appelbaum, F.R., Brown, P.A., Sandmaier, B.M., Storb, R., Fisher, D.R., Shulman, H.M., Graham, T.C., Schuening, F.G., Deeg, H.J., Bianco, J.A. Blood (1992) [Pubmed]

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