SignificanceStandard 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.AimUsing 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.ApproachA 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.ResultsDose-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 2.10×1017±8.24×1016 hν/cm3, whereas Chlorin e6 showed negligible uptake in lung tissue.ConclusionsWe 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.
While the prevalence of central bronchial tumours is declining, that of peripheral lung tumours is increasing. Peripheral lung tumours present either as individual index lesion or as field cancerization, requiring for the former targeting of particular confined volumes of lung tissue versus a therapy for an entire lung or particular lobes thereof. Using FullMonte, a Monte Carlo code; the ability to achieve a tumour selective PDT by transbronchial light source placement was simulated for 525, 665 and 808 nm wavelength. Simulations were executed utilizing in silica models with up to 10 generations of the bronchial tree, tissue photosensitizer concentrations taken from literature or measure in preclinical model systems and tissue optical properties measured with alive ex vivo pig and human lungs perfused with either blood or a transparent low cellular (STEEN) fluid.
The measured effective attenuation coefficients [cm-1] at the three wavelengths for ventilated lungs with either blood 1.26±1.07, 1.93±0.534, 1.09±0.93 or STEEN fluid 1.01±0.873, 0.901±0.318, 0.641±0.31 used as perfusate. When modelling the PDT dose distribution in the lung’s the bronchial air ducts up to the eight generations perturb the fluence considerably.
In all simulations, a dose sufficient to cause necrosis in 98% of the target volume placement of 3 source fibres albeit with various extent of normal lung tumour damage. Full coverage of an entire lung lobe with only three source fibres placed does not provide for effective coverage of the diffuse disease unless a very high selective uptake of the photosensitizer in malignant tissues can be achieved.
The utility to perform treatment planning for transbronchial light delivery is investigated using Monte Carlo simulations. Optical properties of pig and human lungs were determined, and dose volume histograms determined. These dose volume histograms indicate for example the minimum photosensitizer specific uptake ratio required to achieve selective tumour destruction.
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