212Pb/212Bi-EDTMP-Synthesis and biodistribution of a novel bone seeking alpha-emitting radiopharmaceutical

Article abstract of DOI:10.1002/jlcr.2580340805

At present, haematological toxicity is dose limiting in radionuclide therapy of bone metastases, and there is a need for radiopharmaceuticals with improved tumour/bone marrow dose ratios. Therefore, α-emitters e.g. ²¹²Bi may be more suitable than β-emitters, because of the short range and high LET values of α-particIes. In this study, ²¹²Bi and its mother nuclide ²¹²Pb Were produced in an isotope generator by collecting gaseous ²²⁰Rn emanating from barium (²²⁸Th) stearate. The carrier-free ²¹²Pb/²¹²Bi Were bound to the chelating bone-seeking compound ethylene-diamine-tetra(methylene-phosphonic acid) (EDTMP) with 90% yield. The biodistribution in Balb/c mice was investigated by injecting 100 μl of a saline PBS buffer 0.020 M in EDTMP and 10 MBq/ml in ²¹²Pb/²¹²Bi. Mice were killed in groups of three at 0.5, 2, 13 and 24 h post-injection times. Both ²¹²Pb EDTMP and ²¹²Bi-EDTMP localised strongly in the skeleton, especially in the femur, at all time points measured, with the % of injected dose per gram (%ID/g) as high as 15 for ²¹²Pb and 13 for ²¹²Bi. All other organs investigated showed low uptake of both radionuclides, with the exception of the kidneys, for which a ratio femur/kidney of 1.5 for ²¹²Bi 2 h Postinjection was observed. By comparison the ratio femur/blood was 20 for ²¹²Bi 2 h Postinjection. The experiment indicates a potential for ²¹²Pb/²¹²Bi-EDTMP in targeted radiotherapy of osteoblastic bone lesions.