Dose threshold values for endovascular photodynamic therapy (PDT) in normal pig pancreas and human pancreatic cancer

Pancreatic cancers often involve major blood vessels, making complete surgical removal difficult or impossible. We are developing endovascular photodynamic therapy (PDT) as a novel minimally invasive ablation method to clear tumours from these vessels, to enable potentially curative surgery. The goal is to determine the required endovascular irradiation times for effective treatment.

Threshold doses for PDT were estimated using Monte Carlo simulations, based on clinical data from previous Phase I/II studies involving Photodynamic Therapy of pancreatic cancer using interstitial needle-based irradiation. These thresholds were then compared to our recent in vivo study, which used endovascular catheter-based irradiation in a normal pig pancreas. Using these dose thresholds, we estimated the PDT irradiation times needed to achieve necrotic tissue margins of 4-12 mm around blood vessels in pancreatic cancer patients, based on a fixed energy range and increasing doses of photosensitiser.

The threshold dose for Verteporfin-mediated PDT was determined to be 1.43-2.37 × 10¹⁷ hv cm⁻³ for human pancreatic cancer and 1.27 × 10¹⁸ hv cm⁻³ for normal pig pancreas. Based on these values, and assuming homogeneous tissue optical properties and a Verteporfin dose of 0.4 mg kg⁻¹, and an optical power of 300 mW cm^-2 @ 690 nm, necrotic margins of circa 8 mm beyond the vessel adventitia can be anticipated in pancreatic cancer patients. The required irradiation times range from 337 to 636 s, inversely related to vessel diameters of 10 mm and 3 mm, respectively.

These findings suggest that PDT can potentially create a margin around major pancreatic blood vessels free of viable tumour tissue. The calculated dosimetry supports the feasibility of clinical application using the proposed Verteporfin dose and light delivery parameters, warranting further investigation in Clinical trials.