Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer

Br J Cancer. 2018 Nov;119(10):1191-1199. doi: 10.1038/s41416-018-0210-y. Epub 2018 Oct 24.

Abstract

Background: Currently delivered light dose (J/cm2) is the principal parameter guiding interstitial photodynamic therapy (I-PDT) of refractory locally advanced cancer. The aim of this study was to investigate the impact of light dose rate (irradiance, mW/cm2) and associated heating on tumour response and cure.

Methods: Finite-element modeling was used to compute intratumoural irradiance and dose to guide Photofrin® I-PDT in locally advanced SCCVII in C3H mice and large VX2 neck tumours in New Zealand White rabbits. Light-induced tissue heating in mice was studied with real-time magnetic resonance thermometry.

Results: In the mouse model, cure rates of 70-90% were obtained with I-PDT using 8.4-245 mW/cm2 and ≥45 J/cm2 in 100% of the SCCVII tumour. Increasing irradiance was associated with increase in tissue heating. I-PDT with Photofrin® resulted in significantly (p < 0.05) higher cure rate compared to light delivery alone at same irradiance and light dose. Local control and/or cures of VX2 were obtained using I-PDT with 16.5-398 mW/cm2 and ≥45 J/cm2 in 100% of the tumour.

Conclusion: In Photofrin®-mediated I-PDT, a selected range of irradiance prompts effective photoreaction with tissue heating in the treatment of locally advanced mouse tumour. These irradiances were translated for effective local control of large VX2 tumours.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / drug therapy*
  • Dihematoporphyrin Ether / therapeutic use*
  • Female
  • Hot Temperature
  • Mice
  • Mice, Inbred C3H
  • Neoplasms, Experimental / drug therapy*
  • Photochemotherapy*
  • Photosensitizing Agents / therapeutic use*
  • Rabbits
  • Thermometry

Substances

  • Photosensitizing Agents
  • Dihematoporphyrin Ether