Interstitial fluid pressure: A novel biomarker to monitor photo‐induced drug uptake in tumor and normal tissues

Background Low‐dose photodynamic therapy PDT (photoinduction) can modulate tumor vessels and enhance the uptake of liposomal cisplatin (Lipoplatin®) in pleural malignancies. However, the photo‐induction conditions must be tightly controlled as overtreatment shuts down tumor vessels and enhances normal tissue drug uptake. Material and Methods In a pleural sarcoma and adenocarcinoma rat model ( n  = 12/group), we applied photoinduction (0.0625 mg/kg Visudyne®, 10 J/cm 2 ) followed by intravenous Lipoplatin® (5 mg/kg) administration. Tumor and normal tissue IFP were assessed before and up to 1 hour following photoinduction. Lipoplatin® uptake was determined 60 minutes following photoinduction. We then treated the pleura of tumor‐free minipigs with high dose photodynamic therapy (PDT) (0.0625 mg/kg Visudyne®, 30 J/cm 2 , n  = 5) followed by Lipoplatin (5 mg/kg) administration. Results In rodents, photoinduction resulted in a significant decrease of IFP ( P  < 0.05) in both tumor types but not in the surrounding normal lung, equally exposed to light. Also, photoinduction resulted in a significant increase of Lipoplatin® uptake in both tumor types ( P  < 0.05) but not in normal lung. Tumor IFP variation and Lipoplatin® uptake fitted an inverted parabola. In minipigs, high dose photodynamic treatment resulted in pleural IFP increase of some animals which predicted higher Lipoplatin® uptake levels. Conclusion Normal and tumor vasculatures react differently to PDT. Continuous IFP monitoring in normal and tumor tissues is a promising biomarker of vessel photoinduction. Moderate drop in tumor with no change in normal tissue IFP are predictive of specific Lipoplatin® uptake by cancer following PDT. Lasers Surg. Med. 49:773–780, 2017. © 2017 Wiley Periodicals, Inc.