OtherBASIC SCIENCE INVESTIGATIONS

A Nucleolin-Targeted Multimodal Nanoparticle Imaging Probe for Tracking Cancer Cells Using an Aptamer

Do Won Hwang, Hae Young Ko, Jung Hwan Lee, Hyungu Kang, Sung Ho Ryu, In Chan Song, Dong Soo Lee and Soonhag Kim
Journal of Nuclear Medicine January 2010, 51 (1) 98-105; DOI: https://doi.org/10.2967/jnumed.109.069880

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Schematic illustration of steps involved in preparation of MFR-AS1411 and in vitro fluorescence cancer targeting measured by confocal microscopy. MF particles had carboxyl group and Fmoc-protected amine moiety, which was coupled with amine-terminated AS1411 aptamer using EDC (MF-AS1411). After reaction of MF-AS1411 with p-SCN-bn-NOTA, particles were reacted with 67Ga-citrate to form MFR-AS1411.

  • FIGURE 2. 
    FIGURE 2. 

    (A) TEM images were obtained in MF particles consisting of magnetic cobalt ferrite core, rhodamine dye, and MFR-AS1411, which was MF-labeled with AS1411 aptamer and 67Ga-citrate. Uranyl acetate (2%) was used to stain AS1411 aptamer. Dark staining of AS1411 in MFR-AS1411 was detected on surface of MFR-AS1411 particles (uranyl acetate–stained AS1411, black arrow). Scale bar = 50 nm. **P < 0.005. (B) After MF nanoparticles were conjugated with AS1411 aptamer using EDC, MF-AS1411 conjugates were treated into C6 cells. MF-AS1411 specifically targeted C6 glioma cells, as determined by laser scanning confocal microscopy (red, MF-AS1411; blue, 4′,6-diamidino-2-phenylindole dihydrochloride). No fluorescence signal was detected in MF-AS1411mt–treated group.

  • FIGURE 3. 
    FIGURE 3. 

    In vitro cancer targeting using different imaging modalities. (A) C6 cells were treated with diluted concentration of MF-AS1411 (or MF-AS1411mt). Gradual increase of fluorescence intensity in MF-AS1411–treated group was observed, compared with MF-AS1411mt group. (B) After synthesizing MF-AS1411 (or MF-AS1411mt) using p-SCN-bn-NOTA and incubating overnight, MF-AS1411 and MF-AS1411mt were labeled with 67Ga-citrate in buffer solution for 1 h. Concentration of MFR-AS1411 particles was critically dependent on 67Ga radioactivity in C6 cells. *P < 0.05. **P < 0.005. (C) Phantom studies were performed at various concentrations of MFR-AS1411 (or MFR-AS1411mt) mixture. Gradual decrease of MRI signals in MFR-AS1411–treated group were detected, compared with MFR-AS1411mt–treated group, on 1.5-T MRI system.

  • FIGURE 4. 
    FIGURE 4. 

    In vivo multimodal cancer targeting and imaging using MFR-AS1411 particles. (A) MFR-AS1411 particles were intravenously injected into tumor-bearing mice, and radionuclide images were acquired at 1, 6, and 24 h after injection. Scintigraphic images of C6 tumors in mice that received MFR-AS1411 showed that C6 tumors had accumulated MFR-AS1411 at 24 h after injection but did not accumulate MFR-AS1411mt (n = 3). Tumor growth patterns were followed using bioluminescence signals acquired from luciferase-expressing C6 cells. (B) MR images of tumor-bearing mice before and after injection of MFR-AS1411 were acquired. Dark signal intensities at tumor sites were detected in MFR-AS1411–injected mice (arrowhead). (C) Tumors were isolated and their fluorescence verified using IVIS200 system. Fluorescence signal at tumor site injected with MFR-AS1411 was detected, compared with tumors injected with MFR-AS1411mt. Isolated organs in order from upper left to lower right were intestine, liver, spleen, muscle, fat, kidney, stomach, right tumor, left tumor, heart, lung, and tail.

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