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Affibody molecules for in vivo characterization of HER2-positive tumors by near-infrared imaging

Clinical Cancer Research, ISSN: 1078-0432, Vol: 14, Issue: 12, Page: 3840-3849
2008
  • 150
    Citations
  • 0
    Usage
  • 102
    Captures
  • 0
    Mentions
  • 18
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    150
  • Captures
    102
  • Social Media
    18
    • Shares, Likes & Comments
      18
      • Facebook
        18

Article Description

Purpose: HER2 overexpression has been associated with a poor prognosis and resistance to therapy in breast cancer patients. We are developing molecular probes for in vivo quantitative imaging of HER2 receptors using near-infrared (NIR) optical imaging. The goal is to provide probes that will minimally interfere with the studied system, that is, whose binding does not interfere with the binding of the therapeutic agents and whose effect on the target cells is minimal. Experimental Design: We used three different types of HER2-specific Affibody molecules [monomer Z, dimer (Z, and albumin-binding domain-fused-(Z] as targeting agents and labeled them with Alexa Fluor dyes.Trastuzumab was also conjugated, using commercially available kits, as a standard control. The resulting conjugates were characterized in vitro by toxicity assays, Biacore affinity measurements, flow cytometry, and confocal microscopy. Semiquantitative in vivo NIR optical imaging studies were carried out using mice with s.c. xenografts of HER2-positive tumors. Results: The HER2-specific Affibody molecules were not toxic to HER2-overexpressing cells and their binding to HER2 did interfere with neither binding nor effectives of trastuzumab. The binding affinities and specificities of the Affibody-Alexa Fluor fluorescent conjugates to HER2 were unchanged or minimally affected by the modifications. Pharmacokinetics and biodistribution studies showed the albumin-binding domain-fused-(Z -Alexa Fluor 750 conjugate to be an optimal probe for optical imaging of HER2 in vivo. Conclusion: Our results suggest that Affibody-Alexa Fluor conjugates may be used as a specific NIR probe for the noninvasive semiquantitative imaging of HER2 expression in vivo. © 2008 American Association for Cancer Research.

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