Chelator-free synthesis of a dual-modality PET/MRI agent

Objectives This work utilizes the high affinity of superparamagnetic iron oxide nanoparticles (SPION) for positron-emitting radioarsenic (*As) to achieve chelator-free synthesis of a new dual-modality PET/MRI agent. After optimization of radiolabeling conditions and SPION surface modification, the agent was used for dual-modality PET/MRI and lymph node mapping in mice.

Methods *As (*=71,72,74,76) was produced by proton irradiation of GeO₂, chemically isolated, and combined with poly(acrylic acid) (PAA)-modified SPION at pH 7-8. Labeling yield was monitored with thin-layer chromatography. The specificity of labeling was probed by competitive binding studies, and *As-labeling of copper sulfide (CuS) nanoparticles or SPION coated with dense silica (dSiO₂). Serial in vivo PET imaging, lymph node mapping, and biodistribution studies were carried out with *As-SPION, and serial in vivo MRI and lymph node mapping were performed with corresponding “cold” SPION.

Results *As-labeling of SPION was achieved with ~85% yield after 2 h of incubation (>90% yield after 24 h). Citrate ions that can competitively adsorb to SPION could significantly reduce *As-labeling yield, and no *As affinity was observed for control nanoparticles (i.e. SPION@dSiO₂ and CuS), which all confirmed that *As-labeling is specific for SPION surface. PET imaging and biodistribution studies of *As-SPION showed strong liver (as expected for intravenously injected non-targeted nanoparticles) and bladder uptake with the latter due to *As desorption from SPION, which could be effectively reduced by coating *As-SPION with polyethylene glycol (PEG). PET and MRI studies after subcutaneous footpad injection clearly showed high uptake in the ipsilateral popliteal lymph node.

Conclusions *As-SPION is a new PET/MRI agent synthesized by a unique chelator-free chemistry. The labeling is fast, iron-concentration-dependent, and highly specific. Feasibility of in vivo imaging and lymph node mapping was achieved with both PET and MRI. *As-SPION is a promising nanoplatform for future targeted PET/MRI and therapy (when β-emitting ^76/77As is used).