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

Abstract

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/cm2 ) 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/cm2 , 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.

• Authors: Sabrina Cavin, Xingyu Wang, Matthieu Zellweger, Michel Gonzalez, Michaël Bensimon, Georges Wagnières, Thorsten Krueger, Hans-Beat Ris, Fabrizio Gronchi, Jean Y Perentes
• Journal: Lasers in surgery and medicine (Lasers Surg Med) Vol. 49 Issue 8 Pg. 773-780 (10 2017) ISSN: 1096-9101 [Electronic] United States
• PMID: 28544068 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Biomarkers
• Photosensitizing Agents
• Porphyrins
• lipoplatin
• Verteporfin
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, metabolism)
• Animals
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Biomarkers
• Cell Line, Tumor
• Cisplatin (pharmacokinetics, therapeutic use)
• Extracellular Fluid (physiology)
• Injections, Intravenous
• Male
• Photochemotherapy (methods)
• Photosensitizing Agents (therapeutic use)
• Pleural Neoplasms (drug therapy, metabolism)
• Porphyrins (therapeutic use)
• Pressure
• Rats
• Rats, Inbred F344
• Sarcoma (drug therapy, metabolism)
• Swine
• Verteporfin