Bronchoscopic light delivery method for peripheral lung cancer photodynamic therapy

Abstract

Background: Trans-bronchoscope treatment for early stage small peripheral lung cancer, such as photodynamic therapy (PDT), has been investigated. However, despite the efficacy of PDT, light delivery issues limit its application. A method of administering mineral oil with a high refractive index (RI) was previously proposed to enhance light delivery in branched or bent anatomic structures. Lipiodol has a high RI and an exhaustive history of use as a contrast medium for bronchography. We aimed to determine whether the use of lipiodol, like mineral oil, could enhance the illumination effect and therapeutic range of PDT for peripheral lung tumors.

Methods: We injected lipiodol into a pig lung model, guided by a bronchoscope under fluorescent surveillance, to simulate future treatment in humans, and then illuminated with PDT laser fiber to the lipiodol-infused lung to test the technique feasibility in a pig orally administered 20 mg/kg of 5-aminolevulinicc acid (5-ALA) 2 hours before treatment. We also attempted to determine the maximal tolerable light dose in this pilot study for the future studies in human.

Results: We successfully injected lipiodol into peripheral lungs by this technique. The pig could tolerate up to a total of 40 mL of lipiodol and 800 J of red light, without severe acute fetal injury in a non-cancerous lung.

Conclusions: The technique of injecting lipiodol using bronchoscopy under fluorescent guidance was feasible in a pig model. We can apply the guide sheath through bronchoscopy under fluoroscope inspection. Lipiodol can be used as a light diffuser for the peripheral lung tumor PDT model. No severe lethal acute lung injury was caused by this PDT model under careful manipulation. Additional studies evaluating the dose correlation of the photosensitizer and light are needed.

Keywords: Photodynamic therapy (PDT); lipiodol; peripheral lung cancer.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-19-3887). The authors have no conflicts of interest to declare.

2020 Journal of Thoracic Disease. All rights reserved.

Figures

Figure 1

X-ray fluoroscopy image (A) showing lipiodol was instilled into the targeted lung segment through bronchoscopy and placement of the PDT guide sheath (B) for illumination in the lung segment filled with lipiodol. PDT, photodynamic therapy.

Figure 2

Chest radiograph images in the first pig test. The images were taken on the day of operation and then 1st, 7th, 14th, 21st, and 29th day after the operation. Lipiodol 5 mL was infused in each of the four different parts of the left lung (L1-4) and right lung (R1-4). Light was not used in L1/R1 (control group), while frontal light distributor optical fiber and 630 nm Diomed laser was used to provide 200 J (200 mW 1,000 s) light to L2/R2, 400 J (400 mW 1,000 s) to L3/R3, and 800 J (800 mW 1,000 s) to L4/R4. Follow-up chest radiography images in the first pig test show that lipiodol remained for some time in the lung then was gradually absorbed. No severe pneumonia was found at the infusion and illumination dose.

Figure 3

Pigs were sacrificed 1 month after the experiment. The infused lung areas illuminated with different light doses were resected for pathological examination. The results of the pathological examination of L1 and R1 show infusion with lipiodol did not cause damage to the alveolar structure. Only some tissue fluid and inflammatory cell infiltration were noted, indicating that the infusion of lipiodol will not lead to severe pulmonary inflammatory response. With the increase of light energy, the normal lung alveolar structure was gradually damaged. The alveolar structure remained normal under 200 J and 400 J, while moderate inflammatory response was observed under 800 J illumination, although most alveolar structures remained unchanged with no severe necrosis and ulceration. This shows that high-energy PDT (800 J) will cause nonfatal damage to the normal lung. The large arrow shows lung injury with proliferation of myofibroblasts and hemorrhage in the interstitium or alveolar septum. The small arrow indicates lipiodol deposition in lung parenchyma (H&E 100×). PDT, photodynamic therapy.

Figure 4

The second test conducted in triplicates. Lipiodol 5 mL was infused to four different parts in both the left and right lung. No light was given to L1 for the control group, whereas 800 J (800 mW 1,000 s) illumination was given to L2, R1, and R2 using a frontal light distributer optical fiber. Illumination with 800 J energy was successfully conducted in triplicate in both L2 and R1. However, this was terminated in R2 because of the vaporization and combustion caused by overheating of the fiber during illumination. The pig was sacrificed the next day and underwent pathological examination. The examination result showed that the alveolar structures filled with lipiodol (L1, small arrow) and illuminated with 800 J (L2/R1) were generally maintained only some inflammatory cell infiltration (L2/R2, large arrow). However, some inflammatory cell infiltration and interstitial edema persisted, indicating that PDT could still cause acute injury to alveolar structures but not severe necrosis. R2, which shows severe alveolar structural damage and inflammatory tissue infiltration, is the lung tissue damaged by the vaporization and burning of lipiodol (R2, large arrow) (H&E 100×). PDT, photodynamic therapy.

Figure 5

Illumination using 400 mW/cm 500 s (200 J/cm) via a 5-cm cylindrical optic fiber to the lung tissue filled with 5 mL lipiodol did not lead to overheating of the fiber or cause vaporization of the lipiodol. Similar results were obtained in the eight different parts of the two lungs.