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. 2021 Nov 12;8(6):rbab064.
doi: 10.1093/rb/rbab064. eCollection 2021 Dec.

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T 1- T 2 dual-mode magnetic resonance imaging probes

Affiliations

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T 1- T 2 dual-mode magnetic resonance imaging probes

Li Yang et al. Regen Biomater. .

Abstract

The T 1-T 2 dual-mode probes for magnetic resonance imaging (MRI) can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time, making MRI a more flexible imaging modality for complicated applications. In this work, three Gadolinium-diethylene-triaminepentaaceticacid (Gd-DTPA) complex conjugated superparamagnetic iron oxide (SPIO) nanoparticles with different Gd/Fe molar ratio (0.94, 1.28 and 1.67) were prepared as T 1-T 2 dual-mode MRI probes, named as SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67, respectively. All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3+ chelate stability. SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67. SPIO@PEG-GdDTPA0.94 nanocomposites with r 1 (8.4 mM-1s-1), r 2 (83.2 mM-1s-1) and relatively ideal r 2/r 1 ratio (9.9) were selected for T 1-T 2 dual-mode MRI of blood vessels and liver tissue in vivo. Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner. Importantly, one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h. Overall, the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians, e.g. saving time, lowering side effects and collecting data of different organs sequentially.

Keywords: contrast agents; dual-mode imaging; gadolinium; magnetic resonance imaging; superparamagnetic iron oxide.

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Figures

Figure 1.
Figure 1.
Formulation of T1T2 dual-mode contrast agents based on PEG-covered iron oxide conjugated with Gd-DTPA at the peripheral area
Figure 2.
Figure 2.
(a) The XRD pattern of oil-soluble SPIO nanocrystals and (b) FTIR spectra of oil-soluble SPIO (i), SPIO@PEG-GdDTPA0.94 (ii), SPIO@PEG-GdDTPA1.28 (iii) and SPIO@PEG-GdDTPA1.67 (iv)
Figure 3.
Figure 3.
Elemental mapping and EDS of SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67
Figure 4.
Figure 4.
TEM images of OA/SPIO nanocrystals, SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67
Figure 5.
Figure 5.
(a) Hydrodynamic size and (b) zeta potential of SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67 before and after chelation with Gd3+, respectively
Figure 6.
Figure 6.
MR Phantom images of SPIO@PEG-GdDTPA0.94, SPIO@PEG and MagnevistTM at 1.5 T
Figure 7.
Figure 7.
ASIII colorimetric assay of SPIO@PEG-GdDTPA nanocomposites. The absorbance spectra of SPIO@PEG-GdDTPA solution with ASIII at different pH values (7.4 and 5.0) for different incubation time (24 h and 72 h)
Figure 8.
Figure 8.
(a) T1 and T2 imaging of liver on a 3 T clinical MRI scanner at different time points. (b) nSNR = SNRROIs/SNRwater of the liver parenchyma in T1- and T2-weighted images at different time points (n = 3/group)
Figure 9.
Figure 9.
MRA using SPIO@PEG-GdDTPA0.94 as blood pool contrast agents. (a) In vivo MR angiography images of SD rats before and after administration of SPIO@PEG-GdDTPA0.94 at a dose of 0.1 mmol Fe + Gd kg−1, SPIO@PEG and MagnevistTM at a dose of 0.1 mmol Fe or Gd kg−1, respectively. (b) Contrast-enhanced high-resolution vascular details MR image at 15 min post injection of SPIO@PEG-GdDTPA0.94. (c) Quantification of SNR changes in the heart after intravenous injection at different time points (n = 3/group)

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