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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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Histological evaluation of NIR-PIT effect on lung. No apparent damage to the lung was showed by HE-staining at 1 day after NIR-PIT compared to no Tx. Bar = 50 ┬Ám.
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Figure 6: Histological evaluation of NIR-PIT effect on lung. No apparent damage to the lung was showed by HE-staining at 1 day after NIR-PIT compared to no Tx. Bar = 50 ┬Ám.

Mentions: Finally, to assess the effect of repeated NIR-PIT on Calu3-luc-GFP tumor in vivo, GFP fluorescence imaging was performed in both the flank model and pleural disseminated model (Fig. 5A). With the flank model, both GFP/ IR700 fluorescence disappeared at 1 day after NIR-PIT, which was confirmed by ex vivo tumor imaging (Fig. 5B). Using fluorescence thoracoscopy, GFP and IR700 fluorescence disappeared (Fig. 5C and videos S3 and S4 in Additional Files 4-5). A small effusion was observed with thoracoscopy (Fig. 5C arrow). Moreover, there was no apparent damage to the normal lung by NIR-PIT as observed with histological analysis (Fig. 6).


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

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

Histological evaluation of NIR-PIT effect on lung. No apparent damage to the lung was showed by HE-staining at 1 day after NIR-PIT compared to no Tx. Bar = 50 ┬Ám.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Histological evaluation of NIR-PIT effect on lung. No apparent damage to the lung was showed by HE-staining at 1 day after NIR-PIT compared to no Tx. Bar = 50 ┬Ám.
Mentions: Finally, to assess the effect of repeated NIR-PIT on Calu3-luc-GFP tumor in vivo, GFP fluorescence imaging was performed in both the flank model and pleural disseminated model (Fig. 5A). With the flank model, both GFP/ IR700 fluorescence disappeared at 1 day after NIR-PIT, which was confirmed by ex vivo tumor imaging (Fig. 5B). Using fluorescence thoracoscopy, GFP and IR700 fluorescence disappeared (Fig. 5C and videos S3 and S4 in Additional Files 4-5). A small effusion was observed with thoracoscopy (Fig. 5C arrow). Moreover, there was no apparent damage to the normal lung by NIR-PIT as observed with histological analysis (Fig. 6).

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