Isolation of ^(212)Pb from natural thorium for targeted alpha-therapy

摘要

Targeted alpha-therapy(TAT) is increasingly attractive due to its extraordinary antitumor efficacy.However,the supply of α-emitters for TAT is insufficient and under control by a limited number of countries.^(212)Pb is a promising α-emitter with an optimal half-life(10.6 h) and favored decay chain.Of interest,^(212)Pb can be extracted directly from natural thorium,which may be abundant in the mining waste of rare-earth,uranium,etc.Indeed,radioactive thorium waste has been a longstanding environmental challenge that needs immediate action.Developing an on-demand and facile process to isolate ^(212)Pb from natural thorium would be ideal to meet the above challenges,yet is difficult.In theory,the ratio of ^(212)Pb tonatTh is below 10^(-13)in commercially available thorium salts.As a pilot study,2.2 MBq of ^(212)Pb was successfully extracted from a 5 L solution of thorium nitrate by using a Pb-selective resin.The radiochemical purity of ^(212)Pb is over 99.9% according to gamma-ray analysis.The purified^(212)Pb was applied to radiolabel a couple of peptides used in clinics(i.e.PSMA,TATE and FAPI-04),and the radiochemical yields are>85%.Of note,^(212)Pb can be repeatedly separated from the thorium solution every 2 days.In summary,a practical and scalable method was developed to isolate^(212)Pb for potentially clinical use,which may be of great importance as it does not require either cyclotron or nuclear reactor.