Research ArticleBasic Science Investigations

PET Imaging of Tumor-Associated Macrophages with 89Zr-Labeled High-Density Lipoprotein Nanoparticles

Carlos Pérez-Medina, Jun Tang, Dalya Abdel-Atti, Brandon Hogstad, Miriam Merad, Edward A. Fisher, Zahi A. Fayad, Jason S. Lewis, Willem J.M. Mulder and Thomas Reiner
Journal of Nuclear Medicine August 2015, 56 (8) 1272-1277; DOI: https://doi.org/10.2967/jnumed.115.158956

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Structure and composition of rHDL and 89Zr-HDL nanotracers. (A) Schematic of rHDL (left), 89Zr-AI-HDL (middle), and 89Zr-PL-HDL (right). (B) Transmission electron microscopy images of rHDL (left), Zr-AI-HDL (middle), and Zr-PL-HDL (right). (C) Composition (in mol %), size, polydispersity index (PDI), and surface charge of rHDL, 89Zr-AI-HDL, and 89Zr-PL-HDL. Data are presented as mean ± SD (n ≥ 3).

  • FIGURE 2.
    FIGURE 2.

    Radiosynthesis and in vitro stability of 89Zr-HDL nanotracers. Size-exclusion chromatograms showing coelution of plain rHDL (black trace), DFO-apoA-I@rHDL (red trace), and 89Zr-AI-HDL (blue, radioactive trace) (A) and coelution of 1% DSPE-DFO@rHDL (black trace) and 89Zr-PL-HDL (green, radioactive trace) (B). (C) In vitro serum stability of 89Zr-HDL nanotracers at 37°C.

  • FIGURE 3.
    FIGURE 3.

    Pharmacokinetics and biodistribution of 89Zr-HDL nanotracers. (A) Blood time–activity curve for 89Zr-AI-HDL and 89Zr-PL-HDL (n = 3). (B) Radioactivity distribution in selected tissues of 89Zr-AI-HDL (blue) and 89Zr-PL-HDL (green) in mice bearing orthotopic breast cancer tumors, expressed as %ID/g ± SD (n ≥ 3).

  • FIGURE 4.
    FIGURE 4.

    Accumulation of 89Zr-HDL nanotracers in tumor tissues can be visualized by in vivo PET imaging. CT (left) and PET/CT fusion (right) images of 89Zr-AI-HDL (A) and 89Zr-PL-HDL (B) obtained at 24 h after injection in mice bearing orthotopic 4T1 tumors (indicated by arrows).

  • FIGURE 5.
    FIGURE 5.

    89Zr-HDL nanotracers accumulate in TAM-rich areas. Ex vivo histologic analysis of tumor sections at 24 h after administration of HDL nanotracers, showing hematoxylin and eosin (H&E) staining (top left), immunofluorescence for CD31 (top right) and IBA-1 (bottom right), and autoradiography (bottom left) for 89Zr-AI-HDL (A) and 89Zr-PL-HDL (B). Scale bar = 2 mm.

  • FIGURE 6.
    FIGURE 6.

    Both DiO@Zr-PL-HDL and DiO@Zr-AI-HDL preferentially target tumor-associated macrophages. 4T1 cell–induced orthotopic breast tumors were used to isolate single cells. (A) Representative DiO levels in 5 immune cells, namely TAMs, monocyte-derived cells (Mo-derived cells), monocytes, dendritic cells (DCs), and T cells. (B) Representative DiO levels in ECs and tumor cells (4T1). Cells from a phosphate-buffered saline–injected mouse served as controls (gray histograms to left). (C) Quantification of DiO levels presented as mean fluorescence intensity (MFI). Importantly, no statistical significance was found when comparing DiO levels of same cell type from 2 HDL formulations. Statistics were calculated with 2-tailed Student t test with unequal variance by comparing with TAM from same group. **P < 0.01. ***P < 0.001.

Additional Files

Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Bookmark this article

Jump to section

Keywords