Whole body and local hyperthermia enhances the photosensitizing efficacy of 3-[(1'-hexyloxy)ethyl]-3-Devinylpyropheophorbide-a (HPPH)

Abstract

Background and objectives: In this study, we evaluated the impact of hyperthermia in photosensitizing efficacy of 3-[(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH or Photochlor) for the treatment of cancer by photodynamic therapy (PDT).

Study design/materials and methods: The outcome of both whole body hyperthermia (WBH) and local hyperthermia (LH) in combination with HPPH-PDT was determined in BALB/c and nude mice bearing Colon26 and U87 tumors, respectively. LH was performed by using an indigenously designed heating device, that was heated to the required temperature using a circulating water bath. The device which has flexible membrane on one side was placed on skin above the tumor. The temperature of the tumor was monitored using a thermocouple sensor placed on the surface of the tumor capable of measuring the temperature within 0.1°C. Uptake of the photosensitizer in tumors was determined by fluorescence using an IVIS or a Nuance Imaging System. The PDT was performed by exposing the tumors to 665 nm laser loght, (135 J/cm² , 75 mW/cm² ) at the maximal uptake time of HPPH. Tumor size was measured daily using vernier calipers.

Results: The improved PDT efficacy (long-term percentage tumor cure) in combination with hyperthermia is possible due to an increase in tumor-uptake of the photosensitizer (PS), confirmed by in vivo fluorescence imaging and also by increased tumor perfusion and decreased hypoxia as have been reported previously (Sen et al. [2011] Cancer Res. 71:3872-3880 In Vivo. 20:689-695). Interestingly, compared to whole body hyperthermia, the ¹⁴ C- HPPH biodistribution data under local hyperthermia showed similar tumor-uptake in BALB/c mice bearing Colon26 tumors, but significantly lower uptake in other organs and in the blood.

Conclusion: Our study demonstrates that both, fever range whole body and local hyperthermia in combination with HPPH-PDT enhances the long-term tumor cure of BALB/c and nude mice implanted with Colon26 and U87 tumors respectively. Lasers Surg. Med. 50:506-512, 2018. © 2018 Wiley Periodicals, Inc.

Keywords: hyperthermia; photodynamic therapy; photosensitizers.