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

Yaser Hadi Gholami, 1–3 Hushan Yuan, 4 Moses Q Wilks, 4 Richard Maschmeyer, 1 Marc D Normandin, 4 Lee Josephson, 4 Georges El Fakhri, 4 Zdenka Kuncic 1, 2, 5 1Faculty of Science, School of Physics, The University of Sydney, Sydney, NSW, Australia; 2Sydney Vital Translational Cancer Research Centre, St Leonards, NSW, Australia; 3Bill Walsh Translational Cancer Research Laboratory, The Kolling Institute, Northern Sydney Local Health District, Sydney, NSW, Australia; 4Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; 5The University of Sydney Nano Institute, Sydney, NSW, AustraliaCorrespondence: Zdenka Kuncic; Yaser Hadi GholamiSchool of Physics A28, The University of Sydney, Sydney, NSW 2006, AustraliaTel +61 2 9351 3162Fax +61 2 9351 7726Email zdenka.kuncic@sydney.edu.au; yaser.gholami@sydney.edu.auPurpose: 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®, FH) was labeled with the [ 89Zr]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 90Zr-labeled FH was performed by transmission electron microscopy (TEM). Simultaneous PET-MR phantom imaging was performed with different 89Zr-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 [ 89Zr]Zr-FH product was achieved. TEM analysis confirmed the 90Zr atoms adsorption onto the SPION surface (≈ 10% average radial increase). Simultaneous PET-MR scans confirmed the capability of the [ 89Zr]Zr-FH nano-platform for this multi-modal imaging technique. Relative contrast image analysis showed that [ 89Zr]Zr-FH can act as a dual-mode T1/T2 contrast agent. For co-registered PET-MR images, higher spatial resolution (FWHM enhancement ≈ 3) and SNR (enhancement ≈ 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 [ 89Zr]Zr-FH. Additionally, FH is suitable as a dual-mode T1/T2 MR image contrast agent.Keywords: SPIONs, HIR, radiolabeling, MRI, PET, multimodal imaging