Nanomaterial Probes for Nuclear Imaging

Abstract

Nuclear imaging is a powerful non-invasive imaging technique that is rapidly developing in medical theranostics. Nuclear imaging requires radiolabeling isotopes for non-invasive imaging through the radioactive decay emission of the radionuclide. Nuclear imaging probes, commonly known as radiotracers, are radioisotope-labeled small molecules. Nanomaterials have shown potential as nuclear imaging probes for theranostic applications. By modifying the surface of nanomaterials, multifunctional radio-labeled nanomaterials can be obtained for in vivo biodistribution and targeting in initial animal imaging studies. Various surface modification strategies have been developed, and targeting moieties have been attached to the nanomaterials to render biocompatibility and enable specific targeting. Through integration of complementary imaging probes to a single nanoparticulate, multimodal molecular imaging can be performed as images with high sensitivity, resolution, and specificity. In this review, nanomaterial nuclear imaging probes including inorganic nanomaterials such as quantum dots (QDs), organic nanomaterials such as liposomes, and exosomes are summarized. These new developments in nanomaterials are expected to introduce a paradigm shift in nuclear imaging, thereby creating new opportunities for theranostic medical imaging tools.

Keywords: molecular imaging probe; nanomaterials; nanoparticles; nuclear imaging; theranostics.

Scheme 1

Various nanomaterials through modifications for nuclear imaging PET/CT (SPECT/CT) probes.

Scheme 2

Various modifications of nanomaterials as nuclear imaging probes for their multi-functional theranostic applications.

Figure 1

Schematic illustrations of furin-controlled condensation of CBT-⁶⁸Ga and CBT-Ga to yield hybrid oligomers that self-assemble into radioactive nanoparticles CBT-⁶⁸Ga-NPs in furin-overexpressing cancer cells and representative whole-body coronal microPET images of MDA-MB-468 tumor-bearing mice at 1 h post-intravenous injections of 100 µL of 5–12 MBq CBT-⁶⁸Ga and 20 mg/kg CBT-Ga (left) or 5–12 MBq CBT-⁶⁸Ga (right) via tail veins. Reprinted with permission from ref. [23], Copyright 2019 American Chemical Society.

Figure 2

(top) Schematic illustration showing the chelator-free labeling of different types of metal oxides (M_xO_y) with ⁸⁹Zr. (bottom) In vivo radiostability study using PET imaging. (a–e) In vivo maximum intensity projections (MIPs) of mice after i.v. injection of ⁸⁹Zr-M_xO_y-PEG nanomaterials: (a) ⁸⁹Zr-Gd₂O₃-PEG; (b) ⁸⁹Zr-TiO₂-PEG; (c) ⁸⁹Zr-Ta₂O₅-PEG; (d) ⁸⁹Zr-Y₂O₃-PEG), and (e) Free ⁸⁹Zr at different time points. (f,g) Quantitative region of interest (ROI) analysis of the dynamic uptake of ⁸⁹Zr after i.v. injection of ⁸⁹Zr-Gd₂O₃-PEG (f) or free ⁸⁹Zr (g) in bone and liver. (h) Biodistribution of ⁸⁹Zr-Gd₂O₃-PEG and free ⁸⁹Zr measured at 14 days p.i. Data are presented as the percentage of injected dose per gram of tissue (%ID/g): Sk, skin; Mu, muscle; B, bone; Lu, lung; L, liver; K, kidney; Sp, spleen; In, intestine. Error bars are based on the standard error of the mean (SEM) of triplicate samples. Reprinted with permission from ref. [30], Copyright 2017 American Chemical Society.

Figure 3

(top) Schematic of radioiodine labeling of extracellular vesicles. (bottom) In vivo imaging of I-131-Cal62-EVs. After intravenous injection of I-131-Cal-62-EVs (3.7 GBq), gamma camera images were acquired at 1 h, 3 h, 5 h, and 24 h in BALB/c nude mice. The gamma camera images showed intense uptake in liver and spleen areas. There was intense trace accumulation in the bladder. Reprinted from ref. [41].