Search of ligands suitable for 212Pb/212Bi in vivo generators

The short half-life of Bi-212 and Bi-213 limits the application of these radionuclides in alpha radionuclide therapy. The labeling of biomolecules with Pb-212 (mother nuclide of Bi-212) instead of Bi-212 or Bi-213 has the advantage of obtaining a conjugate with a half-life of 10.6 h, compared with of 60 min for Bi-212 or 46 min for Bi-213. Previous attempts to prepare a potential in vivo generator with Pb-212 complexed by the DOTA chelator failed, because about 36 % of Bi was reported to escape as a result of the radioactive decay . Herein, we report studies on the stability of the Pb-212 complexes with eight selected polydentate ligands, which demonstrate high affinity for 3+ metal cations. From the ligand studied DOTP and BAPTA show a sufficient Pb-212 labeling yields but only Pb-212-DOTP complex is stable in isotonic solution of sodium chloride making this way radioactivity level of released Bi-212 is below the limit of detection. It should be emphasized that the DOTP complex is stable only in the case when the concentration of free DOTP exceeds 10(-4) M.