Ethylene diamine tetramethylene phosphonic acid labeled with various β(-)-emitting radiometals: labeling optimization and animal biodistribution.

Skeletal uptake of β(-)-emitting radionuclides may be used for bone pain palliation or myeloablation. The physical characteristics of the β(-) particles required for the two conditions are, however, different, that is, higher energies are favorable for destruction of bone marrow. In this study, the labeling conditions of ethylene diamine tetramethylene phosphonic acid (EDTMP) with three rare earth metals (90Y, 166Ho, and 177Lu) having β(-) particles of diverse physical characteristics were optimized, and their animal biodistributions were studied and compared with 153Sm-EDTMP. All the four radiometals (X =  90Y, 166Ho, 177Lu, and 153Sm) were produced from n,γ reactions of their respective precursors (89Y, 165Ho, 176Lu, and 152Sm). They were labeled with EDTMP at varying degrees of pH and molar ratios, and labeling yields were determined by paper chromatography at each data point. The complexes with optimal labeling yields and their chloride forms (XCl3) were then studied for biodistributions in 66 Sprague-Dawley male rats at 30 minutes, 2 hours, and 24 hours after injection. All the radiopharmaceuticals gave ∼98% complex yields at pH 8. At optimum pH level, good labeling was achieved at X:EDTMP molar ratios of 1:5, 1:8, and 1:20 for 90Y, 166Ho, and 177Lu complexes, respectively. 177Lu-EDTMP showed the best biodistribution results among all the complexes, with a total skeletal uptake of 70.2%  ± 2.4% at 24 hours ((153)Sm-EDTMP = 59.1%  ±  2.6%). 90Y-EDTMP had skeletal accumulation significantly higher than (166)Ho-EDTMP (45.5%  ± 2.9% and 27.4%  ±  3.6%, respectively). Blood activity of all the agents disappeared promptly through the kidneys. This study demonstrates higher localization of 177Lu-EDTMP in skeleton than 153Sm-EDTMP and shows that the localization of 90Y-EDTMP is better among the high-energy radiometals studied.