89Zr-Ferumoxytol iron oxide nanoparticles for multimodality PET/MR lymph node mapping

Objectives The invasion status of lymph nodes (LN) surrounding a tumor is a critical indicator of cancer stage. Multimodality imaging approaches have demonstrated improved accuracy and detectability of sites of disease. We have developed a multimodal PET/MR nanoparticle contrast agent for enhanced detection of LN. For genuine translational potential, we have used an existing approved iron oxide nanoparticle formulation with mild chemical modification for 89Zr radiolabeling.

Methods Iron oxide nanoparticles (ferumoxytol) were modified using carbodiimide chemistry and conjugated to desferoxamine for 89Zr radiolabeling. Axillary LN drainage from the forelimb as well as pelvic drainage following intraprostatic injection in both healthy and Myc-driven transgenic models of prostate cancer were investigated by PET/MR. The signal enhancement of draining nodes by MR and PET imaging was analyzed over 24 h post-injection and correlated to biodistribution and immuno-histochemistry.

Results Modified ferumoxytol displayed 132 amine residues per particle. 89Zr-labeled compound attained a 99.5% or greater purity for, and was stable for 48 h. High-resolution and sensitive imaging of the draining axillary and brachial LN could be made by PET/MR following intradermal forelimb injection. Intraprostatic injections revealed detailed LN drainage networks from the prostate; used to plan surgical excision of the nodes. Subsequent verification of the removal of these nodes was made by ex vivo PET.

Conclusions 89Zr-ferumoxytol enables detailed mapping of LN for pre-operative planning as well as immediate confirmation of successful removal. This indicates that a radiolabeled derivative of an established and clinically approved nanoparticle can be used for high-sensitivity and anatomically specific imaging by PET/MR.

Research Support NIH R25T Molecular Imaging in Oncology Fellowship (5R25CA096945-07) and 2011 SNM Postdoctoral Molecular Imaging Scholar Award.