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Patients with pancreatic adenocarcinoma have a short survival time and many are not eligible for surgery due to vascular proximity or involvement. Hence, downstaging therapies that can effectively clear the tumor from the vessel, are desirable. We hypothesize photodynamic ablation via the endovascular route can effectively clear vessels from such tumor involvement.
To evaluate endovascular light delivery for Photodynamic therapy (PDT) as a potential approach, proof-of-concept studies were performed, including in silico Monte Carlo light simulations, and in vivo, testing in a porcine model. Monte Carlo simulations were carried out in an anatomic realistic model based on segmentation of a porcine pancreas and its blood vessels, where light sources were placed into the superior mesenteric and splenic arteries. Tissue response was evaluated based on the photodynamic threshold model taking local fluence, photosensitizer and tissue sensitivity into consideration. The simulations showed that while limiting the irradiance on the intima to non-thermal levels, pancreatic tissue destruction up to several mm is feasible within clinically acceptable irradiance times for BPD-MA mediated PDT. In vivo studies used normal pigs where pre-and-post PDT contrast-enhanced CT scans (24-48h) were performed to obtain anatomical details and to evaluate gross tissue response. The splenic, hepatic and superior mesenteric arteries were reached via the femoral access route. A guidewire was inserted under fluoroscopy and exchanged with a prototype endovascular catheter for intravascular irradiation. We found it feasible to reach the target areas, however optimal positioning of the irradiators within the prototype catheter was somewhat challenging. Light delivery of several hundreds of J.cm-2 is feasible albeit requiring long irradiation and vessel occlusion times. No vessel perforations were noted on histopathology, however some expected necrosis in smooth muscle cells. The maximum radius of necrosis beyond the vessel's outer diameter reached several mm. This is potentially acceptable for downstaging patients and performing surgical tumor resection.
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