Multimodality PET/MRI agents targeted to activated macrophages - PubMed (original) (raw)

Multimodality PET/MRI agents targeted to activated macrophages

Chuqiao Tu et al. J Biol Inorg Chem. 2014 Feb.

Abstract

The recent emergence of multimodality imaging, particularly the combination of PET and MRI, has led to excitement over the prospect of improving detection of disease. Iron oxide nanoparticles have become a popular platform for the fabrication of PET/MRI probes owing to their advantages of high MRI detection sensitivity, biocompatibility, and biodegradability. In this article, we report the synthesis of dextran-coated iron oxide nanoparticles (DIO) labeled with the positron emitter (64)Cu to generate a PET/MRI probe, and modified with maleic anhydride to increase the negative surface charge. The modified nanoparticulate PET/MRI probe (MDIO-(64)Cu-DOTA) bears repetitive anionic charges on the surface that facilitate recognition by scavenger receptor type A (SR-A), a ligand receptor found on activated macrophages but not on normal vessel walls. MDIO-(64)Cu-DOTA has an average iron oxide core size of 7-8 nm, an average hydrodynamic diameter of 62.7 nm, an r1 relaxivity of 16.8 mM(-1) s(-1), and an r 2 relaxivity of 83.9 mM(-1) s(-1) (37 °C, 1.4 T). Cell studies confirmed that the probe was nontoxic and was specifically taken up by macrophages via SR-A. In comparison with the nonmodified analog, the accumulation of MDIO in macrophages was substantially improved. These characteristics demonstrate the promise of MDIO-(64)Cu-DOTA for identification of vulnerable atherosclerotic plaques via the targeting of macrophages.

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Figures

Fig. 1

FT-IR spectra of (a) MDIO and (b) DIO.

Fig. 2

(a) TEM (top-right corner inset: amplified TEM image (10 nm bar)) of MDIO, and (b) DLS of MDIO and DIO.

Fig. 3

Stability of MDIO-64Cu-DOTA in pH 7.0 trienthanol amine acetate buffer solution over the 48-h time period.

Fig. 4

Mean _T_2 values of cell lysates incubated for 2 h with MDIO (blue, left column) or DIO (red, right column) of different iron concentrations.

Fig. 5

Confocal imaging and T_2_W MRI of blank P388D1 macrophage cells, DIO in P388D1 macrophage cells, and MDIO in P388D1 macrophage cells. ([Fe] = 2 × 10−4 M).

Fig. 6

Competitive uptake of MDIO ([Fe] = 100 μM) and maleylated dextran (blue, left column), dextran sulfate (red, middle), or dextran (yellow-green, right) by P388D1 macrophages.

Fig. 7

Cell viability of P388D1 macrophages after 4-h (blue, left column) or 24-h (red, right column) incubation with different iron concentrations of MDIO.

Scheme 1

Synthesis of macrophage targeted, dual-modality PET/MRI probe MDIO-64Cu-DOTA.

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Multimodality PET/MRI agents targeted to activated macrophages - PubMed (original) (raw)