Background And Aim: Bone-seeking radiopharmaceuticals have been proposed for delivering ablative radiation doses to marrow in multiple myeloma and other haematological malignancies. The aim of this research was to examine the feasibility of labelling ethylenediaminetetramethylenephosphonate (EDTMP) with Dy/Ho as an in vivo generator system and to evaluate whether the in vitro and in vivo stability of Dy-EDTMP and Ho-EDTMP complexes is maintained when the daughter Ho is formed.
Methods: Dy was obtained by neutron irradiation of enriched Dy2O3 in a TRIGA Mark III reactor. Labelling was carried out in an aqueous phosphate medium at pH 8.0 by addition of DyCl3 to EDTMP at a molar ratio 1:1.75. Dy/Ho labelled EDTMP was obtained with a 99.3+/-0.6% radiochemical purity determined by thin-layer chromatography and high-performance liquid chromatography.
Results: In vitro studies demonstrated that Dy/Ho-EDTMP is unstable after dilution in saline and stable in human serum and no translocation of the daughter nucleus occurring subsequent to beta decay of Dy which could produce release of Ho. Biodistribution in mice shows a fast blood clearance after administration of Dy/Ho-EDTMP with a skeletal uptake of 22.32+/-1.86% ID/g at 2 h and 20.12+/-1.94% ID/g after 10 d, a rapid renal elimination and no accumulation in other organs. Theoretical bone marrow absorbed dose calculations indicate that the Dy/Ho-EDTMP in vivo generator system would produce 7.80 times more radiation dose to marrow than that produced by Sm-EDTMP and 3.47 times more than Ho-DOTMP per unit of initial activity retained in the skeleton.
Conclusion: The prepared radiolabelled EDTMP has adequate properties as a stable in vivo generator system for bone marrow ablation.
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