Near infrared photoimmunotherapy prevents lung cancer metastases in a murine model
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Kazuhide Sato1, Tadanobu Nagaya1, Yuko Nakamura1, Toshiko Harada1, Peter L. Choyke1, Hisataka Kobayashi1
1Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1088, USA
Hisataka Kobayashi, e-mail: Kobayash@mail.nih.gov
Keywords: near infrared photoimmunotherapy, metastasis prevention, targeted metastasis treatment, HER2 receptor
Received: February 25, 2015 Accepted: April 30, 2015 Published: May 13, 2015
Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies with the acute toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in preventing lung metastases in a mouse model. Lung is one of the most common sites for developing metastases, but it also has the deepest tissue light penetration. Thus, lung is the ideal site for treating early metastases by using a light-based strategy. In vitro NIR-PIT cytotoxicity was assessed with dead cell staining, luciferase activity, and a decrease in cytoplasmic GFP fluorescence in 3T3/HER2-luc-GFP cells incubated with an anti-HER2 antibody photosensitizer conjugate. Cell-specific killing was demonstrated in mixed 2D/3D cell cultures of 3T3/HER2-luc-GFP (target) and 3T3-RFP (non-target) cells. In vivo NIR-PIT was performed in the left lung in a mouse model of lung metastases, and the number of metastasis nodules, tumor fluorescence, and luciferase activity were all evaluated. All three evaluations demonstrated that the NIR-PIT-treated lung had significant reductions in metastatic disease (*p < 0.0001, Mann-Whitney U-test) and that NIR-PIT did not damage non-target tumors or normal lung tissue. Thus, NIR-PIT can specifically prevent early metastases and is a promising anti-metastatic therapy.
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