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Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience.

Sato K, Nagaya T, Choyke PL, Kobayashi H - Theranostics (2015)

Bottom Line: In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs.Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180).Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1088.

ABSTRACT
Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet is difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of pleural disseminated non-small cell lung carcinoma (NSCLC). In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180). Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease. In conclusion, NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC in mice. Thus, NIR-PIT is a promising therapy for pleural disseminated tumors.

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Characterization of the pleural disseminated NSCLC model. In vivo BLI and fluorescence (GFP/ IR700/ IR800) imaging of Calu3-luc-GFP tumor in flank and pleural disseminated model are shown and demonstrate colocalization of fluorescence. To avoid auto-fluorescence, tra-IR800 was used as well as tra-IR700 for imaging. Fluorescence thoracoscopy demonstrated that pleural metastases had both IR700 and GFP fluorescence signals. APCs were intravenously injected 1 day before the imaging.
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Figure 3: Characterization of the pleural disseminated NSCLC model. In vivo BLI and fluorescence (GFP/ IR700/ IR800) imaging of Calu3-luc-GFP tumor in flank and pleural disseminated model are shown and demonstrate colocalization of fluorescence. To avoid auto-fluorescence, tra-IR800 was used as well as tra-IR700 for imaging. Fluorescence thoracoscopy demonstrated that pleural metastases had both IR700 and GFP fluorescence signals. APCs were intravenously injected 1 day before the imaging.

Mentions: Prior to therapy, implanted thoracic tumors were evaluated with serial fluorescence imaging, BLI and fluorescence thoracoscopy. The implanted thoracic disseminated tumors demonstrated high activity with fluorescence imaging based on IR700, IR800 and GFP, but also high activity on bioluminescence, which co-localized with each other (Fig. 3). Fluorescence thoracoscopy indicated that disseminated tumor establishment and the good contrast of IR700 between tumors and intrathoracic organs (Fig. 3 and Additional File 3: video S2), which confirmed pleural metastases that fluoresced preferentially with tra-IR700. These data suggest that pleural disseminated NSCLC cancer mouse model with Calu3-luc-GFP cells was successfully established; intravenously injection of agent could reach the disseminated tumors.


Near infrared photoimmunotherapy in the treatment of pleural disseminated NSCLC: preclinical experience.

Sato K, Nagaya T, Choyke PL, Kobayashi H - Theranostics (2015)

Characterization of the pleural disseminated NSCLC model. In vivo BLI and fluorescence (GFP/ IR700/ IR800) imaging of Calu3-luc-GFP tumor in flank and pleural disseminated model are shown and demonstrate colocalization of fluorescence. To avoid auto-fluorescence, tra-IR800 was used as well as tra-IR700 for imaging. Fluorescence thoracoscopy demonstrated that pleural metastases had both IR700 and GFP fluorescence signals. APCs were intravenously injected 1 day before the imaging.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4402494&req=5

Figure 3: Characterization of the pleural disseminated NSCLC model. In vivo BLI and fluorescence (GFP/ IR700/ IR800) imaging of Calu3-luc-GFP tumor in flank and pleural disseminated model are shown and demonstrate colocalization of fluorescence. To avoid auto-fluorescence, tra-IR800 was used as well as tra-IR700 for imaging. Fluorescence thoracoscopy demonstrated that pleural metastases had both IR700 and GFP fluorescence signals. APCs were intravenously injected 1 day before the imaging.
Mentions: Prior to therapy, implanted thoracic tumors were evaluated with serial fluorescence imaging, BLI and fluorescence thoracoscopy. The implanted thoracic disseminated tumors demonstrated high activity with fluorescence imaging based on IR700, IR800 and GFP, but also high activity on bioluminescence, which co-localized with each other (Fig. 3). Fluorescence thoracoscopy indicated that disseminated tumor establishment and the good contrast of IR700 between tumors and intrathoracic organs (Fig. 3 and Additional File 3: video S2), which confirmed pleural metastases that fluoresced preferentially with tra-IR700. These data suggest that pleural disseminated NSCLC cancer mouse model with Calu3-luc-GFP cells was successfully established; intravenously injection of agent could reach the disseminated tumors.

Bottom Line: In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs.Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180).Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease.

View Article: PubMed Central - PubMed

Affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1088.

ABSTRACT
Pleural metastases are common in patients with advanced thoracic cancers and are a cause of considerable morbidity and mortality yet is difficult to treat. Near Infrared Photoimmunotherapy (NIR-PIT) is a cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to NIR-light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of pleural disseminated non-small cell lung carcinoma (NSCLC). In vitro and in vivo experiments were conducted with a HER2, luciferase and GFP expressing NSCLC cell line (Calu3-luc-GFP). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized. In vitro NIR-PIT cytotoxicity was assessed with dead staining, luciferase activity, and GFP fluorescence intensity. In vivo NIR-PIT was performed in mice with tumors implanted intrathoracic cavity or in the flank, and assessed by tumor volume and/or bioluminescence and fluorescence thoracoscopy. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. In vivo NIR-PIT led significant reductions in both tumor volume (p = 0.002 vs. APC) and luciferase activity (p = 0.0004 vs. APC) in a flank model, and prolonged survival (p < 0.0001). Bioluminescence indicated that NIR-PIT lead to significant reduction in pleural dissemination (1 day after PIT; p = 0.0180). Fluorescence thoracoscopy confirmed the NIR-PIT effect on disseminated pleural disease. In conclusion, NIR-PIT has the ability to effectively treat pleural metastases caused by NSCLC in mice. Thus, NIR-PIT is a promising therapy for pleural disseminated tumors.

Show MeSH
Related in: MedlinePlus