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

Yaser Hadi Gholami; Hushan Yuan; Moses Q Wilks; Richard Maschmeyer; Marc D Normandin; Lee Josephson; Georges El Fakhri; Zdenka Kuncic

doi:10.2147/IJN.S241971

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

Int J Nanomedicine. 2020 Feb 24:15:1253-1266. doi: 10.2147/IJN.S241971. eCollection 2020.

Authors

Yaser Hadi Gholami^{1

2

3}, Hushan Yuan⁴, Moses Q Wilks⁴, Richard Maschmeyer¹, Marc D Normandin⁴, Lee Josephson⁴, Georges El Fakhri⁴, Zdenka Kuncic^{1

2

5}

Affiliations

¹ Faculty of Science, School of Physics, The University of Sydney, Sydney, NSW, Australia.
² Sydney Vital Translational Cancer Research Centre, St Leonards, NSW, Australia.
³ Bill Walsh Translational Cancer Research Laboratory, The Kolling Institute, Northern Sydney Local Health District, Sydney, NSW, Australia.
⁴ Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ The University of Sydney Nano Institute, Sydney, NSW, Australia.

Abstract

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^®, 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: HIR; MRI; PET; SPIONs; multimodal imaging; radiolabeling.

MeSH terms

Chromatography, Gel
Chromatography, Thin Layer
Contrast Media / chemistry
Ferrosoferric Oxide / chemistry
Humans
Magnetic Resonance Imaging / methods*
Magnetite Nanoparticles / chemistry*
Magnetite Nanoparticles / therapeutic use
Phantoms, Imaging
Positron-Emission Tomography / methods*
Radioisotopes / chemistry
Radiopharmaceuticals / chemistry*
Signal-To-Noise Ratio
Zirconium / chemistry

Substances

Contrast Media
Magnetite Nanoparticles
Radioisotopes
Radiopharmaceuticals
Zirconium
Zirconium-89
Ferrosoferric Oxide

Grants and funding

P41 EB022544/EB/NIBIB NIH HHS/United States