Synthesis of ⁶⁴Cu-Labeled Magnetic Nanoparticles for Multimodal Imaging

TLDR

Complementary imaging modalities, such as MR and PET, provide more information than either alone, motivating the development of dual‑mode probes. The study aims to develop and demonstrate new Cu‑64 coupling methods for dual‑mode PET/MRI nanoparticle probes. The authors synthesized amine‑functionalized polystyrene beads and aldehyde‑modified dextran‑sulfate iron oxide nanoparticles, then coupled them to DOTA‑Cu‑64 via novel chemistries that overcome traditional conjugation failures. Successful labeling achieved 24 % yield on polystyrene beads and 21 % on iron oxide nanoparticles, demonstrating that the new chemistry can be applied to other nanoparticle platforms.

Abstract

Complementary imaging modalities provide more information than either method alone can yield and we have developed a dual-mode imaging probe for combined magnetic resonance (MR) and positron emission tomography (PET) imaging. We have developed dual-mode PET/MRI active probes targeted to vascular inflammation and present synthesis of (1) an aliphatic amine polystyrene bead and (2) a novel superparamagnetic iron oxide nanoparticle targeted to macrophages that were both coupled to positron-emitting copper-64 isotopes. The amine groups of the polystyrene beads were directly conjugated with an amine-reactive form (isothiocyanate) of aza-macrocycle 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10-tetraacetic acid (DOTA). Iron oxide nanoparticles are dextran sulfate coated, and the surface was modified to contain aldehyde groups to conjugate to an amine-activated DOTA. Incorporation of chelated Cu-64 to nanoparticles under these conditions, which is routinely used to couple DOTA to macromolecules, was unexpectedly difficult and illustrates that traditional conjugation methods do not always work in a nanoparticle environment. Therefore, we developed new methods to couple Cu-64 to nanoparticles and demonstrate successful labeling to a range of nanoparticle types. We obtained labeling yields of 24% for the amine polystyrene beads and 21% radiolabeling yield for the anionic dextran sulfate iron oxide nanoparticles. The new coupling chemistry can be generalized for attaching chelated metals to other nanoparticle platforms.