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

• Published in: Lasers in surgery and medicine 2018-07, Vol.50 (5), p.506-512
• Main Authors: Srivatsan, Avinash, Sen, Arindam, Cheruku, Ravindra R., Missert, Joseph R., Durrani, Farukh A., Guru, Khurshid, Pandey, Ravindra K.
• Format: Article
• Language: English
• Subjects: Animals; Calipers; Cancer; Carbon 14; Chlorophyll - analogs & derivatives; Chlorophyll - pharmacology; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; Disease Models, Animal; Effectiveness; Fever; Fluorescence; Hyperthermia; Hyperthermia, Induced - methods; Hypoxia; Lasers; Mice; Mice, Inbred BALB C; Mice, Nude; Organs; Perfusion; Photochemotherapy - methods; Photodynamic therapy; Photosensitization; photosensitizers; Photosensitizing Agents - pharmacology; Skin; Surgical implants; Temperature effects; Temperature requirements; Tumors; Water circulation
• ISSN: 0196-8092; 1096-9101
• DOI: 10.1002/lsm.22932

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 14C‐ 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.