A Radio-Nano-Platform for T1/T2 Dual-Mode PET-MR Imaging

Purpose: This study aimed to develop a chelate-free radiolabeled nanoparticle platform for simultaneous positron emission tomography (PET) and magnetic resonance (MR) imaging that provides contrast-enhanced diagnostic imaging and significant image quality gain by integrating the high spatial resolution of MR with the high sensitivity of PET. Methods: A commercially available super-paramagnetic iron oxide nanoparticle (SPION) (Feraheme((R)), FH) was labeled with the [(89)Zr]Zr using a novel chelate-free radiolabeling technique, heat-induced radiolabeling (HIR). Radiochemical yield (RCY) and purity (RCP) were measured using size exclusion chromatography (SEC) and radio-thin layer chromatography (radio-TLC). Characterization of the non-radioactive isotope (90)Zr-labeled FH was performed by transmission electron microscopy (TEM). Simultaneous PET-MR phantom imaging was performed with different (89)Zr-FH concentrations. The MR quantitative image analysis determined the contrast-enhancing properties of FH. The signal-to-noise ratio (SNR) and full-width half-maximum (FWHM) of the line spread function (LSF) were calculated before and after co-registering the PET and MR image data. Results: High RCY (92%) and RCP (98%) of the [(89)Zr]Zr-FH product was achieved. TEM analysis confirmed the (90)Zr atoms adsorption onto the SPION surface ( approximately 10% average radial increase). Simultaneous PET-MR scans confirmed the capability of the [(89)Zr]Zr-FH nano-platform for this multi-modal imaging technique. Relative contrast image analysis showed that [(89)Zr]Zr-FH can act as a dual-mode T1/T2 contrast agent. For co-registered PET-MR images, higher spatial resolution (FWHM enhancement approximately 3) and SNR (enhancement approximately 8) was achieved at a clinical dose of radio-isotope and Fe. Conclusion: Our results demonstrate FH is a highly suitable SPION-based platform for chelate-free labeling of PET tracers for hybrid PET-MR. The high RCY and RCP confirmed the robustness of the chelate-free HIR technique. An overall image quality gain was achieved compared to PET- or MR-alone imaging with a relatively low dosage of [(89)Zr]Zr-FH. Additionally, FH is suitable as a dual-mode T1/T2 MR image contrast agent.