P-232 - Nanosized crystalline vehicle for targeted radionuclide therapy

Objectives: Interest in targeted radionuclide therapy (TRT) has increased in the last few years leading to the recent approval of Lutathera ([177Lu]Lu-DOTATATE) by the EMA and FDA. Terbium-161 shares similar decay characteristics with lutetium-177, with the simultaneous emission of Auger electrons, thus enhancing the outcome of the therapy.1 In recent years, interest in nanomaterials as the delivery vehicle for TRT has grown as this could overcome several challenges faced by traditional coordination chemistry.2 This study aims to synthesize and evaluate the potential of terbium-161 radiolabeled nanoparticles in targeted radionuclide therapy.
Methods: Two strategies are used to synthesize terbium-161 radiolabeled NaGdF4 nanoparticles. The first method uses the neutron-irradiated 160Gd-enriched Gd2O3 target converted to its trifluoroacetate salt (Gd(CF3CO2)3). Subsequently, the thermolysis of the salt leads to the formation of 161Tb-doped NaGdF4 nanoparticles. The second method is based on the solvothermal synthesis of NaGdF4 using Gd-oleate and [161Tb]TbCl3. The obtained nanoparticles are then covered with a silica shell via a reverse microemulsion process. A polyethylene glycol linker, terminated by a maleimide moiety, is then attached to the surface of the nanoparticles through a silane coupling. Folic acid, coupled with cysteine, is then attached to the end of the linker.
Results: Here, we demonstrate two strategies for the synthesis and radiolabeling of NaGdF4 nanoparticles. Both strategies lead to the formation of a nanoparticles core with a diameter of 13 nm and a NaGdF4:Tb3+ shell of 3 nm. Upon coating with a silica shell, nanoparticles are readily dispersible in aqueous media. Using a combination of crystallographic data, total reflection X-ray fluorescence spectrometry (TXRF), and fluorometric maleimide quantification, the amount of folic acid per nanoparticle can then be determined.
Conclusions: In this work, we show a proof-of-concept study on the synthesis and 161Tb-radiolabeling of NaGdF4 nanoparticles, followed by functionalization with folic acid. Following radiolabeling with higher activity, the biological evaluation of NaGdF4@NaGdF4: [ 161Tb]Tb3+@SiO2-PEG-FA nanoparticles will be carried out.
References: 1. Müller et al., Eur J Nucl Med Mol Imaging 2014, 41 (3), 476–485. 2. Lemaître et al., ACS Appl Nano Mater 2022, 5 (7), 860–8709.