Covalent core-radiolabeling of polymeric micelles with 125 I/ 211 At for theranostic radiotherapy.

Astatine-211 (At) is one of the most promising α-emitters for targeted alpha therapy, especially of cancer metastases. However, the lack of a stable isotope, frequent 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 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 (I) and then adapted for At, enabling the use of both elements as a potential theranostic pair. PMs that were core-radiolabeled with both I or 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 evaluation of the At- labeled PMs, 4-5 % ID/g of the At could still be detected in the blood, showing a promising stability of the PMs. Further, 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 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 At core-radiolabel was observed in the blood.