Photofrin® photodynamic therapy with intratumor photosensitizer injection provides similar tumor response while reducing systemic skin photosensitivity: Pilot murine study

Abstract

Objectives: The goal of this study was to compare tumor response to Photofrin^® photodynamic therapy using intravenous and intratumoral injection of photosensitizer. Systemic skin photosensitivity and photosensitizer distribution were also compared between the two delivery methods.

Methods: SCCVII tumors were initiated in the hind legs of female C3H mice and grown to a volume of ∼1,000 mm³ . Photofrin^® was delivered intravenously via the tail vein at a concentration of 2 mg/kg or intratumorally at concentrations ranging from 0.5-2 mg/kg. A 630 nm laser illumination was delivered via interstitial diffuser placement at a fluence rate of 400 mW/cm and fluence of 100 J/cm. Mice were maintained under normal room lighting for 24 hours after treatment, at which point photographs were captured for assessment of skin photosensitivity. Animals were then sacrificed, and their tumors were excised, sectioned, imaged, and stained with hematoxylin and eosin (H&E). H&E slides were imaged to assess necrosis post-PDT, and skin photographs were evaluated by two blinded reviewers for quantification of skin photosensitivity. Whole-body fluorescence imaging was performed before and after photodynamic therapy.

Results: Tumor necrosis was not significantly different based on treatment group (P = 0.33), while skin photosensitivity was significantly reduced in animals that received Photofrin^® intratumorally (P = 0.0005). Fluorescence imaging revealed similar photosensitizer fluorescence in excised tumors for intratumor and intravenous injection of Photofrin^® (P = 0.48), although fluorescence decreased significantly with decreasing intratumor injection concentration (P= 0.01).

Conclusions: This pilot study shows that intratumoral administration of Photofrin^® has the potential to produce similar tumor outcomes, while reducing systemic skin photosensitivity. Further studies are warranted to characterize and optimize intratumor delivery. Lasers Surg. 50:476-482, 2018. © 2017 Wiley Periodicals, Inc.

Keywords: Photofrin®; intratumor injection; photodynamic therapy; porfimer sodium; skin photosensitivity.