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Tunable and noncytotoxic PET/SPECT-MRI multimodality imaging probes using colloidally stable ligand-free superparamagnetic iron oxide nanoparticles

Authors Pham THN, Lengkeek NA, Greguric I, Kim BJ, Pellegrini PA, Bickley SA, Tanudji MR, Jones SK, Hawkett BS, Pham BTT

Received 9 November 2016

Accepted for publication 16 December 2016

Published 27 January 2017 Volume 2017:12 Pages 899—909

DOI https://doi.org/10.2147/IJN.S127171

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Farooq Shiekh

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

TH Nguyen Pham,1 Nigel A Lengkeek,2 Ivan Greguric,2 Byung J Kim,1 Paul A Pellegrini,2 Stephanie A Bickley,3 Marcel R Tanudji,3 Stephen K Jones,3 Brian S Hawkett,1 Binh TT Pham1

1Key Centre for Polymers and Colloids, School of Chemistry, University of Sydney, 2Radioisotopes and Radiotracers, NSTLI, Australian Nuclear Science and Technology Organisation, Sydney, 3Sirtex Medical Limited, North Sydney, NSW, Australia

Abstract: Physiologically stable multimodality imaging probes for positron emission tomography/single-photon emission computed tomography (PET/SPECT)-magnetic resonance imaging (MRI) were synthesized using the superparamagnetic maghemite iron oxide (γ-Fe2O3) nanoparticles (SPIONs). The SPIONs were sterically stabilized with a finely tuned mixture of diblock copolymers with either methoxypolyethylene glycol (MPEG) or primary amine NH2 end groups. The radioisotope for PET or SPECT imaging was incorporated with the SPIONs at high temperature. 57Co2+ ions with a long half-life of 270.9 days were used as a model for the radiotracer to study the kinetics of radiolabeling, characterization, and the stability of the radiolabeled SPIONs. Radioactive 67Ga3+ and Cu2+-labeled SPIONs were also produced successfully using the optimized conditions from the 57Co2+-labeling process. No free radioisotopes were detected in the aqueous phase for the radiolabeled SPIONs 1 week after dispersion in phosphate-buffered saline (PBS). All labeled SPIONs were not only well dispersed and stable under physiological conditions but also noncytotoxic in vitro. The ability to design and produce physiologically stable radiolabeled magnetic nanoparticles with a finely controlled number of functionalizable end groups on the SPIONs enables the generation of a desirable and biologically compatible multimodality PET/SPECT-MRI agent on a single T2 contrast MRI probe.

Keywords: magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, SPIONs, radiolabeling

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