Multimodality Imaging Agents with PET as the Fundamental Pillar

Abstract

Positron emission tomography (PET) provides quantitative information in vivo with ultra-high sensitivity but is limited by its relatively low spatial resolution. Therefore, PET has been combined with other imaging modalities, and commercial systems such as PET/computed tomography (CT) and PET/magnetic resonance (MR) have become available. Inspired by the emerging field of nanomedicine, many PET-based multimodality nanoparticle imaging agents have been developed in recent years. This Minireview highlights recent progress in the design of PET-based multimodality imaging nanoprobes with an aim to overview the major advances and key challenges in this field and substantially improve our knowledge of this fertile research area.

Keywords: PET; dual-modality imaging; imaging agents; multimodality imaging; nanomedicine.

Figure 1.

Features of the main imaging modalities described in this Minireview.

Figure 2.

a) Schematic illustration of chelator-based radiolabeling of IONPs with ⁸⁹Zr using DFO as a chelator. Reproduced with permission from Ref. ^[22]. Copyright 2014, Nature Publishing Group. b) Schematic illustration of the chelator-free synthesis of *As (or ⁶⁹Ge)-SPIONs. TEM images of SPIONs c) before and d) after transferring them into hydrophilic solutions. e) In vivo lymph node PET imaging with *As-SPION and T₂-MRI with SPIONs. Reproduced with permission from Ref. ^[20]. Copyright 2013, Wiley-VCH.

Figure 3.

a) Actively-targeted PET/T₁-MR dual-modality imaging of tumors with ⁶⁴Cu-Mn₃O₄-TRC105 NPs. Reproduced with permission from Ref. ^[29]. Copyright 2017, American Chemical Society. b) Schematic illustration of the formation of ⁶⁴Cu-MnO NPs. c) Passively-targeting PET/T₁-MR dual-modality imaging of tumors with ⁶⁴Cu-MnO NPs. Reproduced with permission from Ref. ^[28]. Copyright 2010, Royal Society of Chemistry.

Figure 4.

a) Schematic illustration of constructing PET/optical dual-modality imaging nanoprobes. b) Schematic of the hybrid (PET/optical) imaging nanoprobes, C dots, showing the core-containing Cy5 dye and surface-attached PEG chains that bear cRGDY peptide ligands (binding to human α_vβ₃ integrin–expressing tumors) and ¹²⁴I radiolabels. Reproduced with permission from Ref. ^[8b]. Copyright 2014, American Association for the Advancement of Science. c) NP combinations with CL allow improved in vivo imaging (i.e., CL. CRET, and PET imaging). Reproduced with permission from Ref. ^[39]. Copyright 2017, Nature Publishing Group.

Figure 5.

a) Negative-stained TEM image of dried nanonaps. Scale bar, 50 nm. b) Multimodal intestinal transverse plane in a mouse with PA signal (color) and simultaneous US (grey) acquisition following gavage of 100 ODs of nanonaps. c) Nanonap movement in the intestine. Black arrow shows inflow and white arrow shows outflow. d) Nanonap labeling using ⁶⁴Cu. e) Representative PET imaging of nanonaps. 100 ODs of ⁶⁴Cu-labelled nanonaps were gavaged, and mice were imaged at the indicated time points. Scale bars, 1 cm. f) Representative 0.8-mm-thick coronal slices through the mouse, 3 h after gavage. Reproduced with permission from Ref. ^[50]. Copyright 2014, Nature Publishing Group.

Figure 6.

a-c) Schematic illustration of magnetic NPs as matrices to construct PET-based tri-or-more modality imaging nanoprobes. Lower panel in a-c): TEM images of Bi₂Se₃/FeSe₂, IONPs@UCNPs (NaYF₄:Yb/Tm), and IONPs-Au nanostructures, respectively. d) PET/MR/CT/PA tetra-modal imaging with ⁶⁴Cu-Bi₂Se₃/FeSe₂-PEG. a) and d) Reproduced with permission from Ref. ^[9b]. Copyright 2016, Wiley-VCH. b) Fe₃O₄@UCNPs, Reproduced with permission from Ref. ^[58]. Copyright 2016, American Chemical Society. c) IONPs-Au, Reproduced with permission from Ref. ^[59]. Copyright 2013, Elsevier Ltd.

Figure 7.

a) Schematic diagram of the PoP–UCNP structure and ⁶⁴Cu radiolabeling. b) TEM image of Pop-UCNP. High-magnification inset demonstrates the crystalline structure and UCNP core/shell geometry. c) Hexamodal in vivo lymphatic imaging using PoP–UCNPs in mice via fluorescence imaging (FL), upconversion luminescence (UCL) imaging, PET, PET/CT, Cerenkov luminescence (CL) imaging, and photoacoustic (PA) imaging. Reproduced with permission from Ref. ^[9c]. Copyright 2015, Wiley-VCH. d) Schematic diagram of the synthesis of ⁶⁴Cu-MNPs for PET/MRI/PA multimodality molecular imaging of tumors. Reproduced with permission from Ref. ^[66]. Copyright 2014, American Chemical Society.