Multimodal AGuIX® Nanoparticles: Size Characterization by HF5 and Optimization of the Radiolabeling with Various SPECT/PET/Theranostic Tracers

Abstract

Diagnostics that combine imaging techniques such as PET and MRI could enhance disease detection and location if effective multimodal contrast agents can be developed. A nanoparticle called AGuIX has been developed that is comprised of gadolinium-bound by chelates and additional free chelates that can be further labelled with radioactive isotopes enabling both PET and MRI imaging. Herein, we describe the size characterization of these nanoparticles together with their size distribution, which is an important parameter for pharmacokinetics, by a hyphenated method that is hollow fiber flow field flow fractionation (HF5). Once radiolabeled, the size was determined to confirm their integrity. The average radius of these nanoparticles was about 3.5 nm and was not significantly affected by radiolabeling. The labeling of these nanoparticles with radionuclides for SPECT/PET was also evaluated (namely 64Cu, 44Sc and 67Ga). Parameters such as the molar ratio, pH and temperature were optimized. For the three radionuclides considered, 60% to 100% radiolabeling yields were reached, with no further purification at this stage. High specific activities could be attainable for all percentages of free DOTA grafted at the surface of the AGuIX nanoparticles considered in this work.