Covalent core-radiolabeling of polymeric micelles with125I/211At for theranostic radiotherapy

Emanuel Sporer, Christian B.M. Poulie, Tom Bäck, Sture Lindegren, Holger Jensen, Paul J. Kempen, Andreas Kjaer, Matthias M. Herth*, Andreas I. Jensen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Astatine-211 (211At) is one of the most promising α-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 bound211At. 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 (125I) and then adapted for211At, enabling the use of both elements as a potential theranostic pair. PMs that were core-radiolabeled with both125I or211At 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 the211At-labeled PMs, 4-5 % ID/g of the211At could still be detected in the blood, showing a promising in vivo stability of the PMs. Further,211At-labeled PMs accumulated in the spleen (20-30 %ID/g) and the liver (2.5-5.5 %ID/g), along with some detection of211At in the thyroid (3.5-9 %ID/g). This led to the hypothesis that deastatination takes place in the liver, whereas good stability of the211At core-radiolabel was observed in the blood.

Original languageEnglish
JournalNanotheranostics
Volume6
Issue number4
Pages (from-to)388-399
DOIs
Publication statusPublished - 2022

Keywords

  • Alpha-therapy
  • Astatine-211
  • Iodine-125
  • PEG-PLGA
  • Polymeric micelles

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