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

Nanotheranostics

article

Emanuel Sporer¹  Christian B. M. Poulie²  Tom Bäck³  Sture Lindegren³  Holger Jensen⁴  Paul J. Kempen¹  Andreas Kjaer⁴  Matthias M. Herth²  Andreas I. Jensen¹ 

[1] Center for Nanomedicine and Theranostics ,(The Hevesy Laboratory), DTU Health Technology, Technical University of Denmark;Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2;Departments of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg;Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet;National Centre for Nano Fabrication and Characterization, Technical University of Denmark;Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen

关键词: Astatine-211;    polymeric micelles;    PEG-PLGA;    alpha-therapy;    iodine-125;   

DOI  :  10.7150/ntno.71906

学科分类：大气科学

来源: Ivyspring International Publisher

【 摘 要 】

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 bound 211At. 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 for 211At, enabling the use of both elements as a potential theranostic pair. PMs that were core-radiolabeled with both 125I or 211At 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 211At- labeled PMs, 4-5 % ID/g of the 211At 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 of 211At 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 211At core-radiolabel was observed in the blood.

【 授权许可】

CC BY-NC