The Chemical Fate of ²¹²Bi-DOTA Formed by β^- Decay of ²¹²Pb(DOTA)2^-***

Abstract

The increasing use of inert metal complexes in radioimmunotherapy prompted us to explore the potential use of 212 Pb chelates. Herein, we report a study of the chemical fate of the 212 Bi-DOTA complex formed by β' decay of 212 Pb(DOTA) 2~ (H4DOTA = l,4,7,10-tetraazacyclododecanetetraacetic acid). To assure that both parent and daughter complexes were thermally stable, kinetic studies were performed with 203 Pb(II) and 206 Bi(III) which showed that both lead and bismuth complexes with DOTA undergo chemical exchange only very slowly in aqueous solution at pH 4-10.To investigate whether the complex ion which results from decay of 212 Pb(DOTA) 2~ was intact and also stable, solutions initially containing only this ion were analyzed for amounts of DOTA-complexed and uncomplexed 212 Bi after attaining transient equilibrium with 212 Bi. The fraction of 212 Bi radioactivity not complexed to DOTA, vide infra, was found to be 36+2%. This value represents the fraction of breakup of 212 Bi(DOTA)formed from β~ decay of the parent complex. By considering the various extranuclear processes responsible for kinetic and electronic excitation of the 212 Bi daughter, breakup of the 212 Bi-DOTA complex is ascribed to the internal conversion of y-rays emitted by the excited 212 Bi nuclide.

Influence of the Linker on the Biodistribution and Catabolism of Actinium-225 Self-Immolative Tumor-Targeted Isotope Generators

“…Samples of the injectate were used as decay correction standards. Percentage injected dose of 225 Ac per gram of tissue weight (%ID/g) was calculated for each animal at the time of sacrifice, using the equation described previously (33). The mean %ID/g was determined for each experimental group.…”

Production of Endohedral Fullerenes by Ion Implantation

“…One of the potential advantages of the fidlerene for "' Pb versus chelaton is that the fullerene will retain encapsulation of the daughter 2'2Bi. DOTA loses the *I2Bi 36% of the time (Mirzadeh et al, 1993). We were therefore fhstrated to consistently find more ' "Bi in the aqueous portion following a wash than 2'2Pb ( Figure 9).…”

“…While 212Pb is a beta emitter, it is desirable for aparticle RIT because its 10.6 h half-life increases by tenfold the time available to get 212Bi to the target tissue before a-decay. However, while DOTA and other chelators can apparently chelate 212Pb satisfactorily in saline solutions (Mirzadeh et al, 1993 Chong et al, 2006). Furthermore, the internal conversion following 36% of the beta decays to 212Bi also released the daughter from the DOTA.…”

In vivo 212Pb/212Bi generator using indium-DTPA-tagged liposomes

“…Pb sorption was done at pH 5 in an acetate pH buffer solution [13]. 3 . About 7 g of Chelex-100 was loaded on 1.5x8 cm polypropylene columns and preequilibrated with the medium of interest.…”

“…To expand the range of applications, an interesting method is to use its parent, 212 Pb (t 1/2 = 10.6 h), which will generate in vivo 212 Bi. Data in the literature show that the classical chelation approach, used to bind the radionuclides to the carrier molecules, does not work [3]. Although the chelating agent used (DOTA) is known to form strong complexes with both Bi and Pb, a significant part of Bi escapes from the carrier molecule as a result of the radioactive transformation 212 Pb / 212 Bi and the formation of highly ionized daughter atoms after the Auger electrons emission [3].…”