Generation of lead-212 and radioimmunoconjugates for use in cancer therapyand the 'emanating power' of stearates

The emanating power of stearates (i.e. their ability to release radioactive gas generated within them) combined with the diffusivity of this gas, perm it the spatial separation of Pb-212 from its longer lived and thus undesira ble parents. A generator for the alpha -particle emitter Pb-212 is describe d. It features two chambers: separated by a porous septum. A small chamber is loaded with Th-228 carried by barium stearate and a large one contains a powder, which retains recoiling products of radon. The Pb-212 could be har vested daily for therapeutic use with an initial efficacy of over 60% but r adiation damage to the stearate reduced its emanating power after about 3 m onth of continuos operation. The generator, described here, allows for harv esting ultrapure short-lived products and relatively simple workup procedur es. An important assumption concerning the feasability of a Pb-212 complexe d radioimmunoconjugate is that the entrapped Pb-212 can survive the Bi-212 recoil and the 2.24 MEW beta -emission during the Pb-Bi transition. To test this we produced a monoclonal antibody modified organic chealate intermedi ate to which the generator produced Pb-212 has been complexed. We were able to show selective tumor cell cytotoxicity and stability of the conjugate u nder ordinary cell culture conditions. (C) 2001 Elsevier Science B.V. All r ights reserved.