Tuning the lipophilic nature of pyclen-based 90Y3+ radiopharmaceuticals for β-radiotherapy

• Published in: Metallomics Vol. 13; no. 12
• Main Authors: Le Fur, Mariane, Fougère, Olivier, Lepareur, Nicolas, Rousseaux, Olivier, Tripier, Raphaël, Beyler, Maryline
• Format: Journal Article
• Language: English
• Published: England 10.12.2021
• Subjects: Azabicyclo Compounds - chemistry; Ethiodized Oil - chemistry; Ligands; Picolinic Acids - chemistry; Radiopharmaceuticals - chemistry; Radiotherapy - methods; Yttrium Radioisotopes - chemistry; 90Y radiolabeling; internal radiotherapy; picolinate; biodegradable nanoparticles; lipophilicity; Lipiodol; pyclen
• ISSN: 1756-591X
• DOI: 10.1093/mtomcs/mfab070

Pyclen-dipicolinate chelates proved to be very efficient chelators for the radiolabeling with β--emitters such as 90Y. In this study, a pyclen-dipicolinate ligand functionalized with additional C12 alkyl chains was synthesized. The radiolabeling with 90Y proved that the addition of saturated carbon chains does not affect the efficiency of the radiolabeling, whereas a notable increase in lipophilicity of the resulting 90Y radiocomplex was observed. As a result, the compound could be extracted in Lipiodol® and encapsulated in biodegrable pegylated poly(malic acid) nanoparticles demonstrating the potential of lipophilic pyclen-dipicolinate derivatives as platforms for the design of radiopharmaceuticals for the treatment of liver or brain cancers by internal radiotherapy.