Covalent core-radiolabeling of polymeric micelles with <sup>125</sup>I/<sup>211</sup>At for theranostic radiotherapy
Emanuel Sporer, Christian B. M. Poulie, Tom Bäck, Sture Lindegren, Holger Jensen, Paul J. Kempen, Andreas Kjær, Matthias M. Herth, Andreas I. Jensen
Abstract
Astatine-211 ( 211 At) is one of the most promising -emitters for targeted alpha therapy, especially of cancer metastases. However, the lack of a stable isotope, frequent in vivo deastatination, and limited radiochemical knowledge makes it challenging to apply. Here, we report a new strategy for radiolabeling the lipophilic core of polymeric micelles (PMs) with covalently bound 211 At. The PMs were radiolabeled via either an indirect synthon-based method or directly on the amphipathic block copolymer. The radiochemistry was optimized with iodine-125 ( 125 I) and then adapted for 211 At, enabling the use of both elements as a potential theranostic pair. PMs that were core-radiolabeled with both 125 I or 211 At were prepared and characterized, based on a PEG(5k)-PLGA(10k) co-polymer. The stability of the radiolabeled PMs was evaluated in mouse serum for 21 h, showing radiochemical stability above 85%. After in vivo evaluation of the 211 At-labeled PMs, 4-5 % ID/g of the 211 At could still be detected in the blood, showing a promising in vivo stability of the PMs. Further, 211 At-labeled PMs accumulated in the spleen (20-30 %ID/g) and the liver (2.5-5.5 %ID/g), along with some detection of 211 At in the thyroid (3.5-9 %ID/g). This led to the hypothesis that deastatination takes place in the liver, whereas good stability of the 211 At core-radiolabel was observed in the blood.