We recently described a more robust protocol for the oxidation of commercially available stability in human serum, ruling out the other two chelates for in vivo applications. While the ability to chelate [ 201 Tl](III) with sufficient stability required for in vivo applications is promising (though yet to be fully realized), this approach will always be susceptible to in vivo reduction of [ 201 Tl]Tl(III) to [ 201 Tl]Tl(I), and likely subsequent metal dissociation, as has been indicated by the work of Hijnen. We therefore started to explore the possible chelation of "native" [ 201 Tl]Tl(I). This presents some challenges as the monovalent thallium is a very large ion with an ionic radius of 150 pm and, like the alkali metals, its solution chemistry is dominated by aquation. We initially looked at two classes of compounds for which there was some evidence in the literature that suggested potential for radiolabelling [ 201 Tl]Tl(I), crown ethers and cryptophanes.