Search

Background and Objective In this study, we evaluated 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-α (HPPH or Photochlor) as a photosensitizer for the treatment of malignant gliomas by photodynamic therapy (PDT). Study Design/Materials and Methods We performed in vivo reflection spectroscopy in athymic rats to measure the attenuation of light in normal brain tissue. We also studied HPPH pharmacokinetics and PDT effects in nude rats with brain tumors derived from stereotactically implanted U87 human glioma cells. Rats implanted with tumors were sacrificed at designated time points to determine the pharmacokinetics of HPPH in serum, tumor, normal brain, and brain adjacent to tumor (BAT). HPPH concentrations in normal brain, BAT and tumor were determined using fluorescence spectroscopy. Twenty-four hours after intravenous injection of HPPH, we administered interstitial PDT treatment at a wavelength of 665 nm. Light was given in doses of 3.5, 7.5 or 15 J/cm at the tumor site and at a rate of 50 mW/cm. Results In vivo spectroscopy of normal brain tissue showed that the attenuation depth of 665 nm light is ∼30% greater than that of 630 nm light used to activate Photofrin, which is currently being evaluated for PDT as an adjuvant to surgery for malignant gliomas. The t½ of disappearance of drug from serum and tumor was 25 and 30 hours, respectively. Conclusion Twenty-four hours after injection of 0.5 mg/kg HPPH, tumor-to-brain drug ratios ranged from 5:1 to 15:1. Enhanced survival was observed in each of the HPPH/PDT-treated animal groups. These data suggest that HPPH may be a useful adjuvant for the treatment of malignant gliomas. Lasers Surg. Med. 29:397–405, 2001. © 2001 Wiley-Liss, Inc.

Rhodamine 123 (R123)-photochemotoxicity was assessed in BALB/c nude mice bearing a xenografted human squamous cell carcinoma at various power densities and wavelengths and a given incident fluence of 150 Joules/cm2. One hour before light delivery, 1 mg R123/kg was injected i.p. in 20 animals. Surface irradiance was performed on the tumor and an equal size hind leg area of 40 animals. Three groups of 10 animals were treated at 514.5 nm and 0.1 W/cm2, 1 W/cm2, and 30 W/cm2, and one at 488 nm and 30 W/cm2. In each group, five animals received R123. The R123 concentration was measured in the tumor (0.023 ± 0.007 μg/g) and tumor-free tissue (0.023 ± 0.008 μg/g) in three additional animals by high performance liquid chromatography 1 hour after R123-administration. Histologic assessment 72 hours after light delivery revealed no tissue damage at nonthermal power densities, either in the tumor or in the tumor-free tissue, irrespective of R123-administration. At 30 W/cm2, neither in the tumor nor in tumor-free tissues was there any significant difference in the depth of necrosis, irrespective of R123-administration and the wavelength applied. Our results question the validity of R123 as a photosensitizer, at least in this rodent tumor model. © 1993 Wiley-Liss, Inc.