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

Lasers Surg Med. 2017 Oct;49(8):773-780. doi: 10.1002/lsm.22687. Epub 2017 May 22.


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.

Keywords: Lipoplatin®; biomarker; interstitial fluid pressure; photodynamic therapy; pleural malignancies; thoracoscopy.

MeSH terms

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


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