Targeted Alpha Therapy
Targeted alpha radionuclide therapy is a promising modality for cancer treatment due to the short range and high linear energy transfer (LET) of the emitted alpha particles. Bismuth-212 (212Bi) is a well-studied alpha emitter with a short half life time of 1.01 h. As the short half life time of 212Bi makes the direct application difficult, a 212Pb /212Bi in vivo generator was proposed. lead-212 (212Pb) decays to 212Bi through beta minus decay (66.7%) and internal conversion (33.3%). 212Pb has a longer half life time (10.6 h) than 212Bi. Instead of the direct administration of 212Bi, 212Pb is labelled to a carrier and works as the source of 212Bi. It was shown that targeting 212Pb to tumor delivers greater than 10 times the dose per unit of administered activity compared to 212Bi alone. 212Pb is usually applied in the form of a complex by chelators such as DOTA. However, 30% to 40% of the produced 212Bi may be lost due to the internal conversion of 212Pb which can give a maximum energy of 130 eV to a 212Bi atom. This high energy is sufficient to break any chemical bond and results in the release of 212Bi.
In order to prevent the release of 212Bi from the 212Pb /212Bi system, we plan to develop nano-carriers for the encapsulation of 212Pb. The carriers are expected to properly retain the free 212Bi and have good in vivo biodistribution properties.