Irradiance, Photofrin® Dose and Initial Tumor Volume are Key Predictors of Response to Interstitial Photodynamic Therapy of Locally Advanced Cancers in Translational Models

Photochem Photobiol. 2020 Mar;96(2):397-404. doi: 10.1111/php.13207. Epub 2020 Feb 18.

Abstract

The objective of the present study was to develop a predictive model for Photofrin® -mediated interstitial photodynamic therapy (I-PDT) of locally advanced tumors. Our finite element method was used to simulate 630-nm intratumoral irradiance and fluence for C3H mice and New Zealand White rabbits bearing large squamous cell carcinomas. Animals were treated with light only or I-PDT using the same light settings. I-PDT was administered with Photofrin® at 5.0 or 6.6 mg kg-1 , 24 h drug-light interval. The simulated threshold fluence was fixed at 45 J cm-2 while the simulated threshold irradiance varied, intratumorally. No cures were obtained in the mice treated with a threshold irradiance of 5.4 mW cm-2 . However, 20-90% of the mice were cured when the threshold irradiances were ≥8.6 mW cm-2 . In the rabbits treated with I-PDT, 13 of the 14 VX2 tumors showed either local control or were cured when threshold irradiances were ≥15.3 mW cm-2 and fluence was 45 J cm-2 . No tumor growth delay was observed in VX2 treated with light only (n = 3). In the mouse studies, there was a high probability (92.7%) of predicting cure when the initial tumor volume was below the median (493.9 mm3 ) and I-PDT was administered with a threshold intratumoral irradiance ≥8.6 mW cm-2 .

Publication types

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

MeSH terms

  • Animals
  • Dihematoporphyrin Ether / administration & dosage
  • Dihematoporphyrin Ether / therapeutic use*
  • Dose-Response Relationship, Radiation
  • Mice
  • Mice, Inbred C3H
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / therapeutic use*
  • Rabbits

Substances

  • Photosensitizing Agents
  • Dihematoporphyrin Ether