Development of a protocol for whole-lung in vivo lung perfusion-assisted photodynamic therapy using a porcine model.

Abstract

Significance: Standard treatments for isolated lung metastases remain a clinical challenge. In vivo lung perfusion technique provides flexibility to overcome the limitations of photodynamic therapy (PDT) by replacing the blood with acellular perfusate, allowing greater light penetration.

Aim: Using Monte Carlo-based simulations, we will evaluate the abilities of a light delivery system to irradiate the lung homogenously. Afterward, we aim to demonstrate the feasibility and safety profile of a whole-lung perfusion-assisted PDT protocol using 5-ALA and Chlorin e6.

Approach: A porcine model of a simplified lung perfusion procedure was used. PDT was performed at 630 or 660 nm with 5-ALA or Chlorin e6, respectively. Light fluence rate measurements and computed tomography (CT) scan segmentations were used to create in silico models of light propagation. Physiologic, gross, CT, and histological assessment of lung toxicity was performed 72 h post-PDT.

Results: Dose-volume histograms showed homogeneity of light intensity throughout the lung. Predicted and measured fluence rates showed strong reliability. The photodynamic threshold of 5-ALA was $2.10\times {10}^{17}\pm 8.24\times {10}^{16}h\nu /{\mathrm{cm}}^3$ , whereas Chlorin e6 showed negligible uptake in lung tissue.

Conclusions: We lay the groundwork for personalized preoperative in silico dosimetry planning to achieve desired treatment volumes within the therapeutic range. Chlorin e6 demonstrated the greatest therapeutic potential, with a minimal uptake in healthy lung tissues.