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Open Access Highly Accessed Research article

Immediate in vivo target-specific cancer cell death after near infrared photoimmunotherapy

Makoto Mitsunaga1, Takahito Nakajima1, Kohei Sano1, Gabriela Kramer-Marek2, Peter L Choyke1 and Hisataka Kobayashi1*

Author affiliations

1 Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room B3B69, MSC1088, Bethesda, MD, 20892-1088, USA

2 Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

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Citation and License

BMC Cancer 2012, 12:345  doi:10.1186/1471-2407-12-345

Published: 8 August 2012

Abstract

Background

Near infrared (NIR) photoimmunotherapy (PIT) is a new type of cancer treatment based on a monoclonal antibody (mAb)-NIR phthalocyanine dye, (IR700) conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult.

Methods

A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells) was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm2in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm2. Bioluminescence imaging (BLI) was performed before and after PIT.

Results

Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95% immediately after PIT in vivo when light intensity was high (>100 J/cm2), however, in mice receiving lower intensity NIR (50 J/cm2), tumors recurred with gradually increasing BLI signal.

Conclusion

PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo.

Keywords:
Photoimmunotherapy; Theranostics; Cell death; Epidermal growth factor receptor; Molecular targeting; Monoclonal antibody; Bioluminescence imaging