Imaging probe for tumor malignancy

Shotaro Tanaka; Shinae Kizaka-Kondoh; Hasahiro Hiraoka

doi:10.1117/12.808380

20 February 2009 Imaging probe for tumor malignancy

Shotaro Tanaka, Shinae Kizaka-Kondoh, Hasahiro Hiraoka

Proceedings Volume 7190, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications; 719014 (2009) https://doi.org/10.1117/12.808380
Event: SPIE BiOS, 2009, San Jose, California, United States

Abstract

Solid tumors possess unique microenvironments that are exposed to chronic hypoxic conditions ("tumor hypoxia"). Although more than half a century has passed since it was suggested that tumor hypoxia correlated with poor treatment outcomes and contributed to cancer recurrence, a fundamental solution to this problem has yet to be found. Hypoxia-inducible factor (HIF-1) is the main transcription factor that regulates the cellular response to hypoxia. It induces various genes whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important targets of cancer therapy, particularly in therapy against refractory cancers. Imaging of the HIF-1-active microenvironment is therefore important for cancer therapy. To image HIF-1activity in vivo, we developed a PTD-ODD fusion protein, POHA, which was uniquely labeled with near-infrared fluorescent dye at the C-terminal. POHA has two functional domains: protein transduction domain (PTD) and VHL-mediated protein destruction motif in oxygen-dependent degradation (ODD) domain of the alpha subunit of HIF-1 (HIF-1α). It can therefore be delivered to the entire body and remain stabilized in the HIF-1-active cells. When it was intravenously injected into tumor-bearing mice, a tumor-specific fluorescence signal was detected in the tumor 6 h after the injection. These results suggest that POHA can be used an imaging probe for tumor malignancy.

Citation Download Citation

Shotaro Tanaka, Shinae Kizaka-Kondoh, and Hasahiro Hiraoka "Imaging probe for tumor malignancy", Proc. SPIE 7190, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications, 719014 (20 February 2009); https://doi.org/10.1117/12.808380

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KEYWORDS

Proteins

Tumors

Luminescence

Signal detection

Cancer

In vivo imaging

Hypoxia

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