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Published on: May 20, 2020
Evaluation of the spatial diffusion of methylene blue injected in vivo by bronchoscopy into non-small cell lung
Jean-Michel Vignaud1, Olivier Ménard, Nicolas Weinbreck
1Service d'Anatomie Pathologique, Hôpital Central, CHU de Nancy, Nancy, France.
Background:
Due to smoking prevalence and the poor efficiency of current therapy, lung cancer is the leading cause of cancer death in developed countries, and its worldwide incidence is steadily increasing. Gene therapy by direct intratumoral injection of different types of gene constructs through a fiberscope has been suggested and evaluated in a few patients.
Objective:
It was the aim of this study to observe the actual volume of diffusion within a lung tumor using a color marker.
Methods:
Using bronchoscopy, just after anesthesia, methylene blue was injected into patient tumors. These patients subsequently underwent surgery for treatment of a non-small cell lung cancer.
Results:
We observed a diffusion of methylene blue in resected lung tumors with a mean infiltrated versus noninfiltrated tumor volume ratio of 29 +/- 15%. Interestingly, some large tumor areas were not stained. At the cellular level, a preferential diffusion of the dye was observed in the tumor stroma compartment versus the tumor cellular compartment, where basal cells were more frequently and strongly labeled than the other tumor cells.
Conclusions:
Since a cancer is cured when most, if not all, cancer cells are killed, the preliminary evaluation of the spatial diffusion of any injected gene construct should be carried out as a first step in any cancer type.
Insights
Direct injection of gene therapy into lung tumors shows limited diffusion. Methylene blue dye only stained 29% of tumor volume, highlighting the need to assess spatial diffusion before cancer treatment.
Area of Science:
- Oncology
- Pulmonary Medicine
- Gene Therapy
Background:
- Lung cancer is a leading cause of cancer death globally, with increasing incidence and limited treatment efficacy.
- Gene therapy via intratumoral injection is a potential treatment strategy for lung cancer.
- Current gene therapy approaches require understanding of drug delivery and diffusion within tumors.
Purpose of the Study:
- To evaluate the spatial diffusion of injected substances within lung tumors.
- To determine the actual volume of diffusion using a visible color marker.
- To assess the feasibility of intratumoral injection for lung cancer therapy.
Main Methods:
- Bronchoscopic intratumoral injection of methylene blue dye in non-small cell lung cancer patients.
- Patients subsequently underwent surgical resection of the tumors.
- Analysis of dye distribution and stained tumor volume post-surgery.
Main Results:
- Methylene blue dye infiltrated an average of 29% +/- 15% of the resected tumor volume.
- Significant areas within large tumors remained unstained by the dye.
- Preferential diffusion occurred in the tumor stroma, with basal cells showing stronger labeling than other tumor cells.
Conclusions:
- Preliminary assessment of spatial diffusion is crucial for any gene construct intended for cancer treatment.
- Limited diffusion observed suggests challenges for effective gene therapy delivery to all tumor cells.
- Further research is needed to optimize intratumoral delivery methods for lung cancer gene therapy.
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